cabmmcenter for applied biotechnology and

molecular medicine

jahresbericht 2010/2011

yearly report

jahresbericht 2010/2011

yearly report

54

CONTENT

Preface

About Us Steering Committee Scientific Advisory Board 1st CABMM Symposium 1st CABMM Spring Seminar 2nd CABMM Symposium

Portraits Prof. Dr. Dr. Simon P. Hoerstrup Dr. Peter J. Richards Dr. Karin Würtz

Research Reports from the CABMM Research Platform Leading Article Osteoporosis/Leitartikel Osteoporose:

Bone & Stem Cell Research Group Overview CABMM Research Platform:

Cranio-Maxillofacial Surgery and Implantology Group Equine Research Group Interventional Work Research Group Musculoskeletal Research Unit Spine Research Group Tendon Repair Group

CABMM Start-up Grants

Facts and Figures Member Profiles Joint Research Projects Publications

Impressum

6

81012141618

20222630

3436

42424344454849

50

54567074

78

76

vorwor tpreface

Brief eines BeobachtersLetter of an Observer

„Lasset Gelehrte sich zanken und streiten ...“ ( Goethe )

Am CABMM ticken die Weisen jedoch auf einer anderen Stufe. Mit Freude und Achtung werden hier Wissen und La-borfähigkeiten ausgetauscht und so die je eigenen wissen-schaftlichen Ziele gegenseitig ohne Dünkel unterstützt und vorangetrieben.

Dies erklärt mir auch, warum die Startphase dieses Zent-rums nach drei Jahren, trotz trägem Umfeld der UZH, sowohl personell wie einrichtungsmässig im Wesentlichen abgeschlos-sen werden kann.

Es beginnt die hoffentlich wie gewünscht fruchtbare wei-tere Arbeit. Davon berichtet dieses Heft und gewährt uns Einblicke in Erreichtes und Noch-zu-knackendes. Ich freue mich mächtig auf weitere wissenschaftliche Meetings, auf Fei-erstunden und Kontrollgänge.

CABMM vivat, crescat, floreat!Ein Freund des HausesBruno BoninMäxi Stiftung

Liebe Leserin, lieber Leser

“Let the learned men squabble and bicker ...” (Goethe)

But at the CABMM, the wise men and women march to the beat of a different drum. Knowledge and lab skills are readily exchanged in a joyful and respectful manner, thus enabling in-dividuals to promote their own scientific goals in a supportive environment devoid of any unnecessary bad feelings and nega-tive attitudes.

Therefore, it is clear to me why that after only 3 years, the establishment of this center is almost complete, not only re-garding personnel, but also the acquisition of equipment, in spite of the slow moving environment within the UZH.

Hopefully, fruitful work can now begin and thus afford us the opportunity to continue with future endeavors. The reports contained in this booklet allow us insight not only into the ac-complishments, but also the scientific problems that still need cracking. I am very much looking forward to taking part in future scientific meetings, celebrations and inspection rounds.

CABMM vivat, crescat, floreat!A friend of the centerBruno BoninMäxi Foundation

VOrwOrT/prEfaCE

Dear reader,

6

9

Administratively, the CABMM is assigned to the Vetsuisse Faculty of the University of Zurich and consists of the Plenum as highest decision-making body, the Steering Committee as operating body and the Coordinating Office as the central contact and coordination point. Additionally, a Scientific Advi-sory Board was established as controlling body.

The CABMM shows a unique structure, combining (1) a network of existing research groups interested in exchang-ing scientific information and creating collaborations and (2) a working platform for collaborative research, where basic scientists, clinicians and veterinarians are working together shoulder to shoulder for the purpose of developing novel therapeutic approaches for the treatment of dysfunctional and diseased tissue.

The CABMM is dedicated to fostering advances in applied, clinically oriented research in the fields of:

Regenerative medicine Experimental medicine and surgery Applied biotechnology Molecular medicine

The “Center for Applied Biotechnology and Molecular Medicine (CABMM)” is an official com-petence center of the University of Zurich and was founded in 2008 by a small group of highly motivated and successful scientists, namely Prof. Dr. Brigitte von Rechenberg, Prof. Dr. Dr. Simon P. Hoerstrup and Prof. Dr. Dr. Michael O. Hottiger. They pursued the objective to create a stimu-lating environment for interdisciplinary and translational research and thus, to promote scientific exchange and collaborations between basic and clinical researchers.

In terms of scientific exchange and public relations, we are organizing two events every year in parallel with the Scientific Advisory Board (SAB) meetings. During these meetings, all CABMM members, as well as non-members who are inter-ested in the work of our center, have the opportunity to dis-cuss ideas and experiences. Every year in spring, the CABMM Spring Seminar takes place, where senior investigators are given the opportunity to present findings from CABMM-ori-entated research projects. During our CABMM Symposium in autumn, presentations are given which incorporate work related to projects supported by the CABMM start-up grants, projects performed on the CABMM Research Platform and project-related presentations of CABMM members.

Both events are considered to play essential roles in strengthening the CABMM network and enhancing col-laborations between CABMM members from a variety of research disciplines. In addition, these events offer the possi-bility for the SAB to meet with the CABMM members in per-son and to obtain important insights into how the CABMM functions, thus allowing for a more informed opinion of the CABMM’s progress.

In this chapter, the chairwoman of the CABMM Steering Committee, Prof. Dr. Brigitte von Rechenberg, is looking back on the achievements in the reporting period, the CABMM Scientific Advisory Board introduces itself and finally, brief articles about our main events during the last two years can be found.

About us

about uscabmm bodies and events

98

1110

members of cabmm steering committee

Prof. Dr. Brigitte von Rechenberg (Chairwoman),Vetsuisse Faculty, University of Zurich

Prof. Dr. Dr. Michael O. Hottiger (Vice-Chairman),Vetsuisse Faculty, University of Zurich

Prof. Dr. Dr. Simon P. Hoerstrup,Medical Faculty, University of Zurich

Prof. Dr. Annette Liesegang,Vetsuisse Faculty, University of Zurich

Dr. Peter J. Richards,Vetsuisse Faculty, University of Zurich

Dr. Silke MarkVetsuisse Faculty, University of Zurich

Name and affiliation Application field

A – Experimental Medicine and Surgery

B – Molecular Medicine

C – Regenerative Medicine

A – Experimental Medicine and Surgery

C – Regenerative Medicine

Managing Director

About ussteering committee

The accreditation of the CAB-MM has just been renewed, three years after it was estab-lished as an official competence center of the University of Zu-rich. Since its creation, many ac-tivities have unfolded in a very positive way. One of them is the presentation of our first official CABMM yearly report, which is to be edited every alternate year.

Apart from hosting member descriptions and achievements of group members, individual members and group leaders will be introduced on a more personal level. For the first official report, we have started with two platform users and one founding member (see chapter 2 – Portraits).

The CABMM platform and network received a more pro-fessional face through the diligent leadership of our managing director, Silke Mark, PhD, and our scientific director, Peter J. Richards, PhD. They are supported through Marina Klawitter, who joined them last autumn and supports them in all matters of organization and administration. Silke Mark also prepared all documents for reporting our activities and achievements during the last three years, which were highly commended by the “Pro-Rektorat”, responsible for research and develop-ment. Thank you all for your contribution.

While the local platform was very busy with the different groups, also the overall CABMM membership increased to currently 47 members. Together, all of these members have more than 200 young scientists in training, an impressive num-ber for such a novel network community. In addition, two young scientists have completed their habilitation under the umbrella of the CABMM platform. PD Dr. Stefan Stübinger was already accredited last December and Dr. Raffaella San-toro submitted her work to the Vetsuisse Faculty very recent-ly. However, with sadness, we also mourn the loss of one of our early members, Prof. Heike Hall, who succumbed to her disease and passed away much too early leaving her husband and two children behind. We will keep her in good memory and miss her dearly.

from the steering committee of the cabmm

The CABMM held its 1st Spring Seminar in 2011 and two CABMM Symposia in 2010 and 2011, where junior and sen-ior speakers gave lectures about research in their fields of expertise. They were well attended and offered a platform for members to meet and learn about each other’s research interests and available technologies. It served as a starting point for collaborations and common grant applications of which quite a few were successful. Even though the fields of expertise may vary, the same technology for proof of con-cept studies may be required and joint forces give better results. We hope to see even more of this in the near future. Furthermore, regular Journal Clubs and seminars are held for young scientists (Friday 12.30 h – 13.30 h) and soon, the CABMM will also offer modules in biotechnology for gradu-ate students.

The Scientific Advisory Board has been installed consisting currently of seven members. Apart from the Deans of the Vetsuisse and Medical Faculties of the University of Zurich as ex officio members, experienced senior scientists from Can-ada, the Netherlands and Switzerland were chosen and have since put a lot of effort into supporting and improving our network under the guidance of Prof. em Dr. A. Robin Poole. The SAB’s advice was very helpful for the Steering Commit-tee, allowing us to lead the ship through the relatively calm water and shape an attractive future to come.

The first Swiss Center for Regenerative Medicine has opened its doors under the visionary leadership of Prof. Dr. Dr. Simon P. Hoerstrup, one of the founding members of the CABMM. The expertise and sophisticated technology avail-able allowed the Center to be accredited for GMP (Good Manufacturing Practice) in May 2012. The Musculoskeletal Research Unit (MSRU) is striving for GLP (Good Laboratory Practice) for preclinical studies and should be ready to call on Swiss Medic for accreditation this coming autumn, while the University Hospital (USZ) is already accredited for GCP (Good Clinical Practice) studies. The combination of all three accreditation forms will give the University of Zurich a unique position among the European Universities and facilitate re-search from “bench to bedside” for new medical devices and/or technologies as is the overall goal of the CABMM.

Last but not least, the very generous sponsorship of the Mäxi Foundation allowed us to distribute start-up grants for researchers, who want to explore new avenues and/or ex-pand their research field in a new direction. The first results will be presented during the next CABMM Symposium in autumn.

In the name of the Steering Committee of the CABMM I thank all the members for their continuous support and look forward to many prosperous years to come.

Zürich, May 28th, 2012Brigitte von Rechenberg, Prof. Dr. med. vet., Dipl. ECVSHead of the Steering Committee CABMM

1312

About usscientific advisory board

The Scientific Advisory Board of the CABMM, consisting of seven scientists, came into being at the behest of the Steering Committee (SC) of the CABMM. Our mandate is to provide expert guidance and opinion in scientific matters to members of CABMM and its trainees. Our meetings are twice a year coinciding with the receipt of new and revised funding applica-tions to the SC. We report to the SC verbally at the end of each meeting. Subsequently, we supply a written critique and recommendations of all activities that we have reviewed and discussed at the meeting. We attend the symposia of CABMM and contribute to the programs, both in discussions and with presentations.

So who are we? Well, most of us are research scientists with academic affiliations but also with strong interests in the appli-cation of discovery research, while two of us are more related to industrial research and research management. Our experi-ence covers the various fields necessary to evaluate and moni-tor the CABMM including biochemistry, molecular and cell biology, skeletal biology and pathology, bioengineering, tissue repair and nanotechnology. We come from Canada and Eu-rope (Switzerland, The Netherlands). Our experience involves

the scientific advisory board of the cabmm

management of multidisciplinary and translational research pro-grams, their funding and conduct.Our core advisory activities in-clude the review of funding appli-cations and the evaluation of the projects after termination. These tasks involve discussions with all the CABMM members who have currently submitted research pro-posals to the SC. These funding applications are to encourage new innovative projects to be es-tablished in order to accumulate sufficient data to demonstrate feasibility of the proposed re-search. This then acts as a spring-board for full proposals submitted subsequently to national and Eu-ropean funding agencies.

We review differently from most review boards in that we are there to help and guide applicants, to work with them to improve their research, as best we can. Our mandate is also to ensure that the funding proposals conform to the guidelines established by the SC in consultation with the SAB.

We want to ensure that the research is doable: that the neces-sary human resources are available and being utilized within and outside the CABMM; that the research will benefit the applicants and that the money for these “incentive projects” is spent according to the rules of the CABMM and the Mäxi Foundation.

Finally, we are available and enjoy helping trainees and young researchers in their studies wherever we can, both in person and by email. These meetings are one of the highlights of our visits to Zurich.

We are privileged to be a part of the CABMM in helping to ensure creativity and excellence in research, training and de-velopment.

Dr. Bruno Bonin (representative Mäxi Foundation), Dr. Margarete Hoffmann-Amtenbrink, Prof. em. Dr. A. Robin Poole, Dr. Pedro Bittmann, Prof. em. Dr. Peter Sonderegger, Prof. Dr. Frank P.T. Baaijens (from left to right)

members of the cabmm scientific advisory board

Prof. em. Dr. A. Robin Poole (Chairman),McGill University, Montréal, Canada

Prof. Dr. Frank P. T. Baaijens,Eindhoven University of Technology, Eindhoven, The Netherlands

Prof. em. Dr. Peter Sonderegger,University of Zurich, Switzerland

Dr. Pedro Bittmann,Industry (retired), Zurich, Switzerland

Dr. Margarethe Hofmann-Amtenbrink,Industry, Pully, Lausanne, Switzerland

Prof. Dr. Felix R. Althaus, Dean of the Vetsuisse Faculty, University of Zurich, Switzerland

Prof. Dr. Dr. Klaus Grätz,Dean of the Medical Faculty, University of Zurich, Switzerland

Name and affiliation Represented application field

A – Experimental Medicine and Surgery

C- Regenerative Medicine

B – Molecular Medicine

D – Applied Biotechnology

D – Applied Biotechnology

(ex officio)

(ex officio)

1514

Zum ersten Mal seit seiner Gründung im Jah-re 2008 fand am 4. Juni 2010 ein Symposium des CABMM statt. Bereits nach dieser kurzen Anlaufphase umfasste das Zentrum annähernd 30 Mitglieder aus den vier unterschiedlichen Forschungsbereichen Experimentelle Medizin und Chirurgie, Molekulare Medizin, Regenera-tive Medizin und Angewandte Biotechnologie. Während dieser ersten Veranstaltung hatten Mitglieder, deren Mitarbeiter und externe In-teressierte die Gelegenheit, neben zwei Gast-rednern vor allem Vorträge aus den eigenen Reihen zu hören.

Die Konferenz wurde mit einigen einleitenden Worten vom Dekan der Vetsuisse Fakultät der Universität Zürich, Prof. Dr. Felix Althaus, eröffnet. Anschliessend gab der erste Gast-redner, Prof. Dr. Geoffrey Goldspink vom University College in London, einen interessanten Vortrag über die Rolle des Mechano-Wachsumsfaktors (mechano growth factor, MGF) im Gewebe des Bewegungsapparates und der Nervenrepa-ratur. Ein weiterer Höhepunkt war der Übersichtsbeitrag des zweiten Gastredners, Prof. em. Dr. A. Robin Poole von der McGill Universität in Montreal, über das Thema Knorpel und Arthrose.

Nach einer kurzen Kaffeepause gab es anschliessend für einige Mitglieder des Zentrums die Möglichkeit, Einblicke in ihre Forschung zu geben. Der wissenschaftliche Direktor des CABMM Dr. Peter J. Richards eröffnete diesen Teil mit einem Vortrag über die Rolle von Stammzellen in Knochen-

des zentrums für angewandte biotechnologie und molekulare medizin (cabmm)

1. symposium

assoziierten Krankheiten. Einen Überblick über die Regulation von Entzündungsreaktionen auf molekularbiologischer Ebene gab Prof. Dr. Dr. Michael O. Hottiger. Dr. Heike Hall-Bozic erörterte neue Möglichkeiten für die Wundheilung mit Hilfe modifizierter Matrices. Danach gab Prof. Dr. Dr. Simon P. Ho-erstrup eine anschauliche Einleitung in die Anwendung rege-nerativer Medizin bei Herz-Kreislauf-Erkrankungen. Einen de-taillierteren Einblick in die vaskuläre Forschung ermöglichte Dr. Zsolt Kulcsar von der Hirslanden Klinik. Er referierte über den Blutfluss und seiner wichtigen Rolle bei Aneurysmen im Gehirn. Darüber hinaus konnte PD Dr. Colin Schwarzwald, PhD, das Themengebiet der Herz- und Gefässmedizin unter Berücksichtigung des Pferdes als Tiermodell abrunden.

In ihren Schlussbemerkungen bedankte sich Prof. Dr. Brigitte von Rechenberg – Vorsitzende des Leitungsausschus-ses des CABMM – bei allen Vortragenden, die das erste Symposium unseres Zentrums zu einer erfolgreichen Kon-ferenz machten. Weiterhin betonte sie, dass die Vernetzung der unterschiedlichen Bereiche innerhalb des CABMM das prioritäre Ziel sei.

Am Ende dieses erfolgreichen Symposiums hatten die Teil-nehmer während eines Apéro Gelegenheit für den wissen-schaftlichen Austausch in angenehmer Atmosphäre.

of the center for applied biotechnology and molecular medicine (cabmm)

1st symposium

The first Symposium of the CABMM took place on June 4th, 2010 and was attended by CABMM members representing the four dif-ferent application fields of the CABMM: Ex-perimental Medicine and Surgery; Molecular Medicine; Regenerative Medicine; Applied Bio-technology; as well as their group members and other interested people. During this first meet-ing, all attendees had the opportunity to listen to talks given by international guest speakers as well as by local scientists within the CABMM framework.

The Dean of the Vetsuisse Faculty of the University of Zu-rich, Prof. Dr. Felix Althaus, opened the proceedings. Subse-quently, the first guest speaker, Prof. Dr. Geoffrey Goldspink from the University College in London, gave an interesting lec-ture about the role of mechano growth factor (MGF) in mus-culoskeletal tissue and nerve repair. This was then followed by a talk given by the second guest speaker, Prof. em. Dr. A. Robin Poole from the McGill University in Montreal, who gave a very well informed overview of some of the mechanisms governing cartilage and degenerative joint disease.

After a short coffee break, a selection of CABMM mem-bers had the opportunity to present work related to their

own research fields. Dr. Peter J. Richards, scientific director of the CABMM, opened this session with a talk about the role of stem cells in bone disease. This was followed by a presentation given by Prof. Dr. Dr. Michael O. Hottiger who gave an overview of the regulatory mechanisms of inflamma-tion at the molecular level. Subsequently, Dr. Heike Hall-Bozic discussed the potential of advanced modified matrices for wound healing. Prof. Dr. Dr. Simon P. Hoerstrup followed by giving an insightful presentation on the clinical applications of cardiovascular regenerative medicine. Both Dr. Zsolt Kulcsar (Hirslanden clinic, Zurich) and PD Dr. Colin Schwarzwald, PhD (University of Zurich), continued on the topic of cardio-vascular research, by giving stimulating talks related to both human and animal medicine.

In her concluding remarks, the chairwomen of the CABMM, Prof. Dr. Brigitte von Rechenberg, thanked all speakers for their interesting presentations and for making the first meet-ing a great success. Furthermore, she pointed out the major goal: networking between the different research fields within the CABMM.

The meeting was brought to a close by all participants join-ing together to enjoy an apéro, which allowed everyone to discuss important scientific topics and to strengthen collabo-rations within the CABMM.

About us1. symposium/1st symposium

1716

Am 11. Mai 2011 hat das CABMM zu seinem ersten Spring Seminar geladen. Ziel dieser Ver-anstaltung war es, Einblicke in die Forschung verschiedener Mitglieder des Kompetenzzent-rums zu gewinnen und somit den wissenschaft-lichen Austausch und Kollaborationen inner-halb des CABMM zu fördern.

Das Seminar wurde von der Vorsitzenden des Leitungs-ausschusses, Prof. Dr. Brigitte von Rechenberg, eröffnet. Sie begrüsste Redner aus den Bereichen der regenerativen Me-dizin, molekularen Medizin und der experimentellen Medizin und Chirurgie.

Prof. Dr. Anton Fürst eröffnete den ersten Teil der Veran-staltung mit einem Vortrag über subchondrale Knochenzysten bei Pferden. Danach gab Prof. Dr. Marcy Zenobi-Wong eine Übersicht über den Einfluss der Umgebung, unterschiedlicher Zellkultursysteme und verschiedener Biomaterialien auf die Knorpelregeneration. Anschliessend präsentierte Dr. Pao-lo Cinelli Aspekte zur Aufrechterhaltung der Pluripotenz in Stammzellen.

Den zweiten Teil startete Prof. Dr. Jess Snedeker mit ei-nem Vortrag über Sehnenverletzungen und deren Heilung, wobei er vielversprechend die Biomechanik mit Aspekten der Biologie kombinierte. Dr. Caroline Ospelt repräsentier-te anschliessend die Gruppe von Prof. Dr. Steffen Gay und erörterte die Schlüsselrolle synovialer Fibroblasten während der rheumatoiden Arthritis und den Einfluss epigenetischer Faktoren auf diese Krankheit. Während des letzten Vortrages verdeutlichten Prof. Dr. Norbert Boos und Dr. Karin Würtz die Wichtigkeit des Zusammenspiels zwischen Klinik und Grundlagenforschung. Sie sprachen über molekulare Ereig-nisse bei Rückenschmerzen und veranschaulichten dabei, wie Wissen aus der Klinik die tägliche Laborarbeit und wie im Gegenzug Resultate aus der Forschung die klinische Betrach-tungsweise beeinflussen können.

Mit einigen abschliessenden Worten beendete Prof. Dr. Brigitte von Rechenberg unser erstes Spring Seminar. Sie be-tonte, dass der Austausch zwischen Wissenschaftlern unter-

des zentrums für angewandte biotechnologie und molekulare medizin (cabmm)

1. spring seminar

schiedlicher Forschungsgebiete innerhalb des CABMM sehr wichtig sei und weiterhin vorangetrieben werden soll.

Schliesslich hatten die Teilnehmer während eines Apéro Gelegenheit für wissenschaftliche Diskussionen in angeneh-mer Atmosphäre.

of the center for applied biotechnology and molecular medicine (cabmm)

1st spring seminar

On May 11th, 2011, the 1st CABMM Spring Seminar took place at the University of Zurich. The aim of this event was to gain insight into the research performed by several CABMM members and thereby, promote scientific ex-change and collaborations within the CABMM network.

The seminar was opened by the chairwomen of the CABMM, Prof. Dr. Brigitte von Rechenberg. She introduced speakers from the fields of regenerative medicine, molecular medicine as well as experimental medicine and surgery.

Prof. Dr. Anton Fürst started the first session with a pres-entation about subchondral cystic lesions in horses. Subse-quently, Prof. Dr. Marcy Zenobi-Wong gave an overview of the influence of the environment, different cell culture sys-tems and diverse biomaterials on cartilage repair. This was

followed by a presentation by Dr. Paolo Cinelli concerning the maintenance of pluripotency in stem cells.

The second session started with Prof. Dr. Jess Snedeker who talked about tendon injury and healing, combining bio-mechanics and biological sciences. Afterwards, Dr. Caroline Ospelt - representing the group of Prof. Dr. Steffen Gay - discussed the key role of synovial fibroblasts during rheuma-toid arthritis and highlighted how changes in the epigenome may influence the disease. During the last presentation, Prof. Dr. Norbert Boos and Dr. Karin Würtz demonstrated the importance of translational research by speaking about the interplay between clinics and basic science. They talked about molecular events during back pain and how clinical knowl-edge could influence daily lab work and vice versa..

Prof. Dr. Brigitte von Rechenberg closed our 1st Spring Seminar with some concluding remarks. She highlighted the importance of scientific exchange between researchers from different research fields, which should be further encouraged within the network of the CABMM.

Finally, an apéro was offered at the end of the event, giv-ing all participants the opportunity for such discussions in a relaxed atmosphere.

About us1. spring seminar/1st spring seminar

1918

Am 17. November 2011 fand das zweite Sym-posium des CABMM statt. Über 70 Teilnehmer aus der gesamten Schweiz und dem Ausland hatten die Möglichkeit, interessante Vorträge von Wissenschaftlern aus dem CABMM-Netz-werk zu hören.

Prof. Dr. Brigitte von Rechenberg – Vorsitzende des Lei-tungsausschusses des CABMM – begrüsste die Zuhörer und führte durch den ersten Teil des Symposiums. Unter dem Motto „CABMM start-up grants“ gab Prof. em. Dr. A. Robin Poole von der McGill Universität, Montreal, Canada nützliche Informationen aus seiner langjährigen Erfahrung zum erfolg-reichen Schreiben und der Beurteilung von Forschungsan-trägen. Durch Dr. Peter J. Richards und seinem Vortrag über die Rolle von Serinproteasen in der Bandscheibendege-neration wurde anschliessend zum ersten Mal ein Projekt vorgestellt, welches durch einen CABMM Start-up Grant finanziert wurde.

Von Prof. Dr. Dr. Michael O. Hottiger vorgestellt, eröffnete Prof. Dr. Ohad Medalia den zweiten Teil des Symposiums mit einem Vortrag über die Methodik der Cryo-Elektronen-Mik-roskopie und begeisterte das Publikum mit äusserst beein-druckenden Aufnahmen „from the nuclear periphery to cell adhesion“. Das Anwendungsgebiet der molekularen Medizin unseres Zentrums wurde daraufhin von Dr. Sascha Beneke mit interessanten neuen Aspekten über die Methode der Chromatin Immunopräzipitation repräsentiert.

Den letzten Teil dieses Events mit Vorträgen aus den Ge-bieten „Regenerative Medizin“ und „Experimentelle Medizin und Chirurgie“ moderierte der wissenschaftliche Direktor des CABMM, Dr. Peter J. Richards. Prof. Dr. Michael Blauth vom Universitätsspital Innsbruck, Österreich gab eine er-frischende Übersicht über das Gebiet der Osteoporose und die damit verbundenen klinischen Probleme. Neueste Erkenntnisse aus dem Bereich der Prävention von Herzin-farkten wurden von Dr. Chad Brokopp erläutert. Prof. Dr. Benjamin Gantenbein von der Universität Bern beendete die Vortragsreihe mit einem ansprechenden Vortrag über Regenerationsprozesse in der Bandscheibe.

des zentrums für angewandte biotechnologie und molekulare medizin (cabmm)

2. symposium

Mit den abschliessenden Worten von Prof. Dr. Brigitte von Rechenberg konnte ein weiteres, sehr erfolgreiches Meeting mit angesehenen Wissenschaftlern aus den Gebieten der An-gewandten Biotechnologie und molekularen Medizin beendet werden.

Beim folgenden Apéro hatten die Anwesenden schliesslich die Gelegenheit, in angenehmer Atmosphäre ihre Forschung zu diskutieren und Kollaborationen auszubauen.

of the center for applied biotechnology and molecular medicine (cabmm)

2nd symposium

The 2nd CABMM Symposium took place on November 17th, 2011. More than 70 participants from both here in Switzerland and also from abroad, had the opportunity to listen to inter-esting presentations given by scientists con-nected to the CABMM network.

Prof. Dr. Brigitte von Rechenberg – chairwomen of the CABMM – opened the meeting by introducing the first speak-er, Prof. em. Dr. A. Robin Poole from the McGill University, Montreal, Canada. He gave some useful insights into the writ-ing and review of research grants based on his many years of experience. Subsequently, Dr. Peter J. Richards presented the results from one of the first projects to be funded by a CABMM start-up grant, a study investigating the role of serine proteases in spinal disc degeneration.

Introduced by Prof. Dr. Dr. Michael O. Hottiger, Prof. Dr. Ohad Medalia opened the second session of the symposium with an exciting talk about about cryo-electron microscopy, and amazed the audience with some impressive images. Rep-resenting the field of molecular medicine, Dr. Sascha Beneke then gave a lecture on the technique of chromatin-immuno-precipitation and highlighted important new aspects associ-ated with this field of research.

The last session was chaired by the scientific director of the CABMM, Dr. Peter J. Richards, and covered the fields of regen-erative medicine and experimental medicine and surgery. Prof. Dr. Michael Blauth from the University Hospital of Innsbruck, Austria, gave an insightful and thought provoking overview of

osteoporosis and associated clinical problems. Dr. Chad Bro-kopp then presented his latest data regarding the prevention of myocardial infarction. Finally, Prof. Dr. Benjamin Gantenbein from the University of Bern, ended the session by giving a well structured account of his current work in the area of interver-tebral disc regeneration.

With the concluding words of Prof. Dr. Brigitte von Rechen-berg, another very successful meeting with reputable scientists from the fields of applied biotechnology and molecular medi-cine could be closed.

During the apéro that followed, all participants had the op-portunity to discuss scientific questions and to strengthen col-laborations within the CABMM network.

About us2. symposium/2nd symposium

2120

Behind every person there is also a personal story, but in the demanding business environment of daily work there is often not much time left to get to know each other very well on a private level. However, private and work life are always connected and one influences the other. That is why we decided to introduce two to three people connected to the CABMM network with a personal portrait in every yearly report, describing not only their scientific interests, but also some private aspects of their life.

Paula Lanfranconi, free journalist, interviewed the following three people for this years’ report:

Prof. Dr. Dr. Simon P. Hoerstrup Co-founder of the CABMM Member of the CABMM Steering Committee Head of the Swiss Center for Regenerative Medicine

Dr. Peter J. Richards Scientific director of the CABMM Member of the CABMM Steering Committee Head of the Bone and Stem Cell Research Group at the CABMM Loving husband and father

Dr. Karin Würtz Head of the Spine Research Group at the CABMM CABMM platform user since its creation Sports fan

For those who are not yet familiar with the portrayed peo-ple, this may be a good opportunity to gain insight into their research and also to learn about their private life and person-ality. For those who already know these people in person, it may be still possible to learn something new about them. And for all readers, it may be interesting to recognize the parallels between their work and private life.

Portraits

20

por traits

2322

Professor Simon P. Hoerstrup, 45, hat das CABMM mitbegründet. Er ist wissenschaftlicher Abteilungsleiter am Zentrum Chirurgie und zu-dem Leiter des Zentrums für Regenerative Me-dizin der Universität und des Universitätsspitals Zürich. Im Bereich Tissue Engineering hat er ein Stück Medizingeschichte mitgeschrieben.

Auf den ersten Blick sieht der grosse Bildschirm in seinem Büro aus wie ein Aquarium. Eben schwimmt ein blassrosa We-sen heran. Auf dem Kopf trägt es eine Art Geweih. „Ein Axolotl, unser neues Maskottchen“, sagt Simon Hoerstrup und schmun-zelt. Dieser altertümliche südamerikanische Lurch, erfährt man, sei ein Spezialist für das Regenerieren von Körperzellen: „Man kann ihm eine Extremität entfernen und innerhalb weniger Tage hat sie sich erneuert.“

Schon sind wir mitten im Thema. Simon Hoerstrup ist kom-munikativ, easy going. Sein Thema ist die regenerative Medizin. „Wir lassen uns“, erläutert er, „von den Mechanismen der Na-tur inspirieren und nutzen zum Beispiel Stammzellen, um Or-ganschäden oder Krankheiten zu behandeln.“ Seine Hauptmo-tivation sei eine ärztliche: „Meine Forschung soll den Patienten zugute kommen.“ Vor wenigen Wochen ist er zusammen mit seinem Team in das von ihm initiierte erste Schweizerische Zentrum für Regenerative Medizin eingezogen. An diesem Vormittag läuft dort ein spannender Versuch: Chirurgen aus Hoerstrups Gruppe setzen einem Schaf eine Herzklappe ein, die sie aus körpereigenen Zellen des Tieres im Labor gezüchtet hatten. Das Schaf stammt aus der Klinik der Vetsuisse-Fakultät. „Die Tierklinik“, sagt Simon Hoerstrup, „ist für uns ein wichti-ger Forschungspartner.“ Seit der Gründung des CABMM in-tensivierte sich die enge Zusammenarbeit noch. Ihr Ziel: Das CABMM sollte sich zu einer integrativen Forschungsplattform mit höchsten Standards entwickeln, die auch Forschende aus anderen Disziplinen nutzen können.

Seine Ausbildung absolvierte Simon Hoerstrup in der Schweiz, in Deutschland und in den USA. Sein besonderes In-teresse galt der Kinderherzchirurgie. Ein anspruchsvolles Metier, eigentlich eine Kunst: „Jeder kindliche Herzfehler ist anders. Man kann häufig keine standardisierten Verfahren anwenden.“ Mitte

simon p. hoerstrup, portrait von paula lanfranconi

„meine forschung soll den patienten zugute kommen“

der 1990er Jahre entschied Simon Hoerstrup, sich dem damals neuen Gebiet des Tissue Engineerings zuzuwenden: „Der Be-darf für künstlich gezüchtete, lebende Gewebe ist gross, gerade in der Kinderherzchirurgie.“ Rund ein Prozent aller Neugebore-nen kommt mit einem Herzfehler zur Welt, und viele Patienten benötigen eine chirurgische Intervention. Das Frustrierende dabei: die heutigen Gefäss- und Herzklappenprothesen wach-sen nicht mit. Bis die kleinen Patienten erwachsen sind, müssen sie deshalb mehrfach operiert werden – mit steigendem Risiko und viel frühem Leid.

Wer Simon Hoerstrup zuhört, bekommt ein Stück Medizin-geschichte mit. Er war an der Harvard Medical School als Post-doc federführend dabei, als man in Boston die weltweit ersten im Labor gezüchteten lebenden Herzklappen im Tiermodell testete. Zurück in Zürich, schrieb er ein weiteres Kapitel dieser Erfolgsgeschichte: Seine Gruppe konnte erstmals beim Schaf beweisen, dass im Labor aus körpereigenen Zellen gezüchtete Blutgefässe tatsächlich mitwachsen.

Er ist ein spannender Erzähler. Und ein anschaulicher dazu. Er legt ein kunstvolles Gebilde auf den Tisch: Das Gerüst einer Herzklappe, geformt aus einem pergamentfarbenen Filz. Diesen abbaubaren Filz besiedeln die Forscher mit den Zellen des zu operierenden Tieres. Im Bioreaktor stimulieren sie diese Zellen, sodass sie in den Filz einwachsen und ein neues Gewebe bil-den. Diese mitwachsende Herzklappe kann man künftig auch mit einem Katheter minimal invasiv in den Körper implantieren.

Bald schon steht Hoerstrups Team vor einem wichtigen Durchbruch. Im Schafmodell sehen die Langzeitresultate mit aus körpereigenen Zellen gezüchteten Blutgefässen viel ver-sprechend aus. Für eine erste Anwendung beim Kind indes sind die Anforderungen ungleich höher. Und die Zeit drängt: Damit am Herzen keine Folgeschäden entstehen, sollte das ge-züchtete Gewebe nach der Geburt raschmöglichst implantiert werden. Um Zeit zu gewinnen, hat Hoerstrups Gruppe ein Verfahren entwickelt, mit dem sie schon während der Schwan-gerschaft Stammzellen des Kindes gewinnen können. Wann genau sein Team das erste Neugeborene operieren wird, lässt der Forscher offen: „Ich möchte betroffenen Eltern keine ver-frühten Hoffnungen machen.“

Als sein „zweites Baby, neben der Grundlagenforschung“ bezeichnet Simon Hoerstrup den Aufbau und die Leitung des Schweizerischen Zentrums für Regenerative Medizin. Vor sechs Jahren hatte er es initiiert – als zukunftsfähige translationale Forschungsstätte für die wachsende Zahl von Wissenschaftlern und Medizinern, die auf Zelltherapien setzen. Für künstlich ge-züchtete Gewebe sind die regulatorischen Zulassungshürden, die Good Manufacturing Practice, hoch: Sie gelten als Arznei-mittel und müssen die entsprechenden Tests durchlaufen – eine hoch gerüstete Infrastruktur, die nun im neuen Zentrum für Regenerative Medizin bereit steht.

Das CABMM spielt hier eine wichtige Rolle. „Das Span-nende“, so Hoerstrup, „ist ja, dass CABMM-Mitbegründerin Brigitte von Rechenberg an der Vetclinic gerade eine tierex-perimentelle Einheit aufbaut, welche den Normen für Good Laboratory Practice entspricht.“ Dank des neuen Zentrums, so Hoerstrup, seien nun alle präklinischen und klinischen For-schungsstandards an der Universität Zürich erfüllt. Ein weiterer wichtiger Standortvorteil. „Und“, fügt Hoerstrup bei, „dank dieser nun geschlossenen Kette geht die akademische Kontrol-le über unsere Forschung nicht mehr frühzeitig an die Industrie verloren.“

Simon Hoerstrup scheint die Zeit vergessen zu haben. Er klickt auf ein Bild. Es zeigt kleine Bälle, gebildet von rund 5000 Zellen: So genannte Mini Beating Hearts, die in orchestrier-ter Form schlagen und so klein sind, dass man sie nach einem Myokardinfarkt mit dem Katheter in den Herzmuskel injizie-ren und diesen so regenerieren kann. Auch dies, sagt Simon Hoerstrup mit einer Prise Vaterstolz, sei eine Methode, die sein Team entwickelt habe: „Brillante junge Wissenschafter, die nicht nur die Laborarbeit beherrschen, sondern aufgrund ih-res medizinischen Hintergrundes neue Therapien auch klinisch umsetzen können.“ Solche translationalen Talente möchte er noch stärker fördern.

In ein paar Jahren, wenn das Zentrum für Regenerative Me-dizin auf Kurs ist und sein Team die ersten Neugeborenen er-folgreich mit künstlich gezüchteten Gefässen und Herzklappen versorgt hat, möchte der heute 45-Jährige nochmals in neue Gebiete wie z.B. die Epigenetik einsteigen, „den so genannten zweiten Code“. Er findet es faszinierend, dass man laut jüngster epigenetischer Forschungsergebnisse seine Gene eben doch durch den Lebensstil direkt beeinflussen könne und diese „er-worbenen Genveränderungen“ sogar vererbbar seien.

In wenigen Wochen werden die Aquarien mit dem Axolotl angeliefert, dem Maskottchen des Zentrums für Regenerati-ve Medizin. Bis dann soll auch der Meetingraum wohnlicher ausgestaltet sein. Am langen Tisch treffen sich dann, vielleicht nach einer durchgearbeiteten Nacht, Chirurgen, Zellbiologen, Ingenieure zum Morgenkaffee. „So“, sagt Simon Hoerstrup mit blitzenden Augen, „entstehen neue Ideen. Das macht Spass!“

Portraitssimon p. hoerstrup

2524

Professor Simon Hoerstrup, 45, co-founded the CABMM. He is the scientific director of the Department of Surgery as well as head of the Swiss Center for Regenerative Medicine of the University and the University Hospital Zurich. In the field of tissue engineering, he participat-ed in writing a part of medical history.

At a first glance, the big screen in his office looks like an aquarium. Just now, a pinkish creature draws near. On its head, it has some sort of antlers. “An axolotl, our new mascot” says Simon Hoerstrup with a smile. This ancient amphibian from South America, one learns, is a specialist in regenerating body cells: “One can remove a limb and within only a few days, it is renewed.”

Yet, we are in the middle of the topic. Simon Hoerstrup is communicative, easy going. His topic is regenerative medi-cine. “We allow ourselves”, he explains, “to be inspired by the mechanisms of the nature and use for example stem cells for the treatment of damaged organs or diseases. His main moti-vation is of a medical nature: “My research should be for the benefit of the patients”.

simon p. hoerstrup, portrait by paula lanfranconi

“my research should be for the benefit of the patients”

A few weeks ago, he moved together with his team into the first Swiss Center for Regenerative Medicine that he initiated. This morning, a fascinating experiment is running: surgeons of Hoerstrup’s team insert a cardiac valve in a sheep that was generated in the lab from the animals’ own body cells. The sheep is from a clinic of the Vetsuisse faculty. “The animal hospital”, says Simon Hoerstrup, “ is an important research partner for us.” Since the founding of the CABMM, the close collaboration has been intensified even further. The aim: The CABMM should develop into an integrative research plat-form with the highest standards that could also be used by researchers from other disciplines.

Simon Hoerstrup completed his education in Switzerland, Germany and the USA. His special interest is pediatric car-diac surgery. A demanding profession, rather an art: “Every infantile cardiac defect is different. Often, it is not possible to apply a standardised technique.” In the middle of the nineties, Simon Hoerstrup decided to turn toward the field of tissue engineering, which was still new at this time: “The need for artificially generated, living tissues is high, especially in pediatric cardiac surgery.” About one percent of all newborns are born with a cardiac defect; many of these patients need a surgical intervention. The frustrating part: today’s vascular and cardiac valves prostheses are not growing. That’s why the small pa-tients have to be operated on several times until they reach maturity – with an increasing risk and a lot of suffering at their young age.

Who listens to Simon Hoerstrup, experiences a part of medical history. As a post doc at the Harvard Medical School, he was one of the leading people when in Boston the world-wide first living cardiac valves that were cultured in the lab were tested in an animal model. Back in Zurich, he wrote another chapter of this success story: His group could show for the first time in sheep that blood vessels generated in the laboratory from the body’s own cells could grow with the individual after re-implantation.

He is a fascinating narrator ; and a very descriptive one as well. He puts an artful object on the table: the scaffold of a heart valve formed by a parchment-coloured felt. On this

resorbable felt, the researcher cultures the cells derived from the animal to be operated. In a bioreactor, the cells are stimu-lated in such way that they grow into the felt and form a new tissue. In the future, this growing heart valve will be implanted in the body minimally invasive using a catheter.

Hoerstrup’s team is on the verge of a breakthrough. In the sheep model, the long-term results of blood vessels gener-ated from the body’s own cells are very promising. However, the requests for a first application in children are much higher. And time is short: In order to avoid complications, the cul-tured tissue should be implanted as soon as possible after birth. To gain time, Hoerstrup’s group developed a method to be able to harvest stem cells of the child already during pregnancy. The researcher leaves open when exactly his team will operate on the first newborn: “I don’t want to raise any false hopes in the concerned parents.”

Simon Hoerstrup describes the buidling-up and direction of the Swiss Center for Regenerative Medicine as his “second baby beside basic research”. Six years ago, he initiated the centre – as a future-compliant translational research facility for the growing number of scientists and doctors that count on cell therapies. For artificially generated tissues, the regula-tory barrier, the Good Manufacturing Practise, is high: They belong to medicinal/pharmaceutical products and have to pass the corresponding tests – a well prepared infrastructure

that is now available at the new Swiss Center for Regenera-tive Medicine.

Hereby, the CABMM plays an important role. “The exciting thing is”, says Hoerstrup, “that the CABMM co-founder Bri-gitte von Rechenberg is currently establishing a unit for animal experimentation fulfilling the requirements of Good Labora-tory Practice.” According to Hoerstrup, thanks to the new centre, all preclinical and clinical research standards would be implemented at the University of Zurich. Another important advantage of the location. “And”, adds Hoerstrup, “ thanks to this complete quality chain, the academic control over our research is not taken by industry at an early stage.”

Simon Hoerstrup seems to forget about the time. He clicks on a picture. It shows small balls, formed by approximately 5’000 cells: so-called mini beating hearts that are beating in an orchestrated way and that are so small that they can be inject-ed with a catheter into the heart muscle in order to regener-ate it after a myocardial infarct. Also this method, says Simon with a pinch of pride of a father, would have been developed by his team: “Brilliant, young scientist that do not only know about how to work in the lab, but can bring new therapies into the clinics due to their medical background.” He would like to promote even more translational talents such as these.

In a few years, when the Swiss Center for Regenerative Medicine is up and running and his team has successfully treated the first newborn with artificially generated vessels and heart valves, the now 45years-old would like to get once more into new fields like epigenetics, “the so-called second code”. He finds it fascinating that according to recent epige-netic research results it can be possible to directly influence genes by ones lifestyle and that this “acquired genetic change” can even be inheritable.

In a few weeks, the aquariums with the axolotl will be delivered, the mascot of the Swiss Center for Regenerative Medicine. Until then, the meeting room should also be more comfortably equipped. At the long table – perhaps after a night worked through – surgeons, cell biologists and engineers will meet to have their morning coffee. “So”, says Simon Hoerstrup, his eyes sparkling with joy, “ new ideas develop. That’s fun!”

Portraitssimon p. hoerstrup

2726

Ohne Herzblut läuft bei ihm gar nichts: Pe-ter J. Richards, Wissenschaftlicher Direktor des CABMM und Leiter der Gruppe Knochen- und Stammzellforschung. Er sieht durchaus Paralle-len zwischen seiner Aufgabe als Forschungsleiter und jener als Vater.

Er ist ein bisschen verspätet, das Laborgespräch mit seiner Gruppe dauerte länger. Doch jetzt ist er da: Peter J. Richards, 41, ein gross gewachsener Mann mit blaugrauen Augen, einer guten Portion Humor und ebenso viel forscherischem Herzblut. Sei-ne tägliche Arbeit? „Prüfen, was meine drei Mitarbeitenden der Knochen- und Stammzellgruppe tun, neue Ideen einbringen, Publikationen schreiben.“ Und Geld einwerben. Am Anfang, be-kennt er, sei ihm dieser Teil seiner Arbeit schwer gefallen, Geld bedeute ihm persönlich nicht sehr viel. „Für mich ist Denken wichtig und Forschen.“

Er war aus der Industrie gekommen, hatte sich mit Rücken-markforschung befasst. Richtig glücklich sei er in der angewand-ten Forschung aber nicht geworden. Es gab zu viele fixe Vorga-ben und zu wenig Platz für eigene Ideen. Er müsse, sagt er, mit dem Herzen dabei sein. „Ich sehe mich als Entdecker. Ich wache am Morgen auf, habe eine Idee und sage: Vielleicht ist sie gut, probieren wir sie aus!“

Jetzt, als Wissenschaftlicher Direktor des CABMM mit seinen unterschiedlichen Forschungsbereichen kann er sein breites Wissen über Arthrose, Osteoporose und Arteriosklerose ein-bringen, wissenschaftliche Inputs geben. Sein Hauptgebiet hier ist die Knochen- und Stammzellforschung. Seine Gruppe will die zellulären Prozesse besser verstehen, die sich in osteoporo-tischen Knochen abspielen. Ultimatives Ziel sind neue Behand-lungsmöglichkeiten.

Zur Zeit therapiert man Osteoporose hauptsächlich mit Bis-phosphonaten. Doch es gibt Probleme bei der Langzeitbehand-lung: Nach zehn, 15 Jahren entwickeln sich bei vielen Patienten Kiefernekrosen. Eine andere, hoch wirksame Therapie ist Para-thormon (PTH), ein Peptidhormon, welches die Knochenbil-dung steigert. Aber auch hier gibt es Hürden: bisher konnte Pa-rathormon nur injiziert werden. Inzwischen versucht man auch,

peter j. richards, portrait von paula lanfranconi

„ich sehe mich als entdecker“

diese Schwierigkeit mit einem PTH-Nasenspray zu überwinden. „Das Hauptproblem bei osteoporotischen Knochen“, er-

läutert der Forscher, „ist, dass sie brüchig sind, weil ihre Kno-chenstammzellen zuviel Fett- und zu wenig Knochengewebe generieren.“ Das Spezielle: Sein Team arbeitet mit Stammzellen aus Fettgewebe. Es gebe da nämlich ein Paradox: Wenn man Stammzellen aus Fettgewebe stimuliert, entwickeln sie Kno-chengewebe. „Viel effizienter, als es Knochenstammzellen tun. Das ist super – in vitro.“ In einem nächsten Schritt wird die Gruppe Stammzellen in osteoporotische Mäuse implantieren, in der Hoffnung, dass es dereinst auch beim Menschen funktio-niert, vielleicht sogar prophylaktisch, zum Beispiel bei Hochrisi-kopatienten. Doch bis dahin ist noch ein weiter Weg.

Peter J. Richards betrachtet Osteoporose aber nicht bloss mit dem nüchternen Blick des Forschers: „Wenn ich auf der Stras-se alten Menschen begegne, geht mir manchmal der Gedanke durch den Kopf, dass diese Person in wenigen Jahren stürzen und einen Knochenbruch erleiden könnte.“ Möglicherweise mit fatalen Folgen, immerhin stirbt einer von drei Betroffenen inner-halb des ersten Jahres nach dem Sturz an Komplikationen wie Lungenentzündung.

Er selber habe sich noch nie etwas gebrochen. Sein einzi-ger Unfall, erzählt er amüsiert, sei ein Sturz vom elterlichen

Sofa gewesen. „Ich war sechs, dachte, ich sei Superman – und sprang.“ Wie schmerzhaft ein Knochenbruch sein kann, erlebte der junge Vater kürzlich am Beispiel seiner Tochter Lucy. Die Vierjährige hatte zu Weihnachten Skis geschenkt bekommen. Die ersten Versuche im Schnee machten Spass. Doch dann war Lucy gestürzt. Und schrie aus Leibeskräften. „Schrecklich für uns Eltern!“ Der Arzt röntgte. Ein sauberer Bruch. Lucy bekam ei-nen Gips. Den habe sie recht lustig gefunden, weil man darauf malen konnte. Nach vier, fünf Wochen war der Knochen wieder heil und der Unfall fast vergessen.

Der Wissenschafter staunt, wie stark seine beiden Kinder Lucy, 4 und Lisa, 1, sein Leben verändert hätten. „Früher“, sagt er, „war die Arbeit, das Labor, alles für mich, vom Morgen bis zum Abend.“ Er stammt nicht aus einem wissenschaftlichen Umfeld. Sein Vater war Pilot bei der australischen Marine, die Mutter Ergotherapeutin. Als er sieben war, zog die Familie nach England. Er war gut in Biologie, machte einen PhD in Immunologie. Doch es war noch nicht das Richtige, er machte noch Postdocs in Immunologie und Zellbiologie.

In die Schweiz, nach Zürich, war Peter J. Richards letztlich der Liebe wegen gekommen. Er hatte sich an der Universität von Wales in eine Doktorandin verguckt – Sandra. Sie wollte nach dem Studienabschluss zurück nach Konstanz, in die Nähe ihrer Eltern. Die beiden jungen Forscher fanden eine Stelle in der Schweiz, Peter J. Richards am Universitätsspital Zürich. Dort befasste er sich bereits mit Stammzell- und Osteoporosefor-schung. Lange, sagt er, sei er kein Familienmensch gewesen, habe seine freie Zeit lieber auf dem Surfbrett verbracht. Mit kleinen Kindern wäre das nicht mehr so einfach gewesen. „Aber als

das Baby da war, sagte ich mir : Statt surfen kannst du auch jog-gen, da kommt dein Gehirn in eine Art Trance.“ Ausgehen oder Kino, seine zweite grosse Leidenschaft, sind ihm inzwischen nicht mehr so wichtig.

Wenn er abends nach Hause kommt, freuen sich die Kin-der. „Meistens jedenfalls.“ Lucy, die Vierjährige, trägt bereits zur Verbesserung von Daddys Deutsch-Vokabular bei. Am Anfang, räumt er ein, sei es ihm schwer gefallen, Familie und Beruf un-ter einen Hut zu bringen. Als Wissenschaftlicher Direktor des CABMM hat er ein 150 Prozent-Pensum. „Ich liebe einen ge-wissen Stress“, sagt er. Oft sitze er auch abends zuhause noch am Computer. Nicht gerade zur Freude von Partnerin Sandra, die ihr 60 Prozent-Pensum in einer Biotechnologiefirma mit ei-ner anderen jungen Mutter teilt. „Aber“, sagt er lachend, „ich versuche, es nicht überhand nehmen zu lassen.“

Er sieht durchaus Parallelen zwischen seiner Aufgabe als Vater und seiner Arbeit als Forschungsleiter: Auch in der Wissenschaft gebe es kaum Kurse, wo man lernen könne, wie man Leute an-leiten soll. Mit seinen Kindern ergehe es ihm ganz ähnlich.

Wo sieht sich Peter J. Richards in fünf Jahren? „Hoffentlich immer noch in der Forschung!“, antwortet er. Und vielleicht sei er dann Professor. Mit seiner breiten wissenschaftlichen Aus-richtung ist es allerdings nicht einfach, ein Habilitationsthema zu finden. Doch Professor zu werden, relativiert er, sei nicht sein einziges Ziel. Er hofft, in Zukunft noch mehr Publikationen schreiben zu können und mehr Geld für das CABMM einzu-werben, damit es sich zu einem grossen Zentrum entwickeln könne.

Die spannenden Fragen werden Peter J. Richards noch eine Weile nicht ausgehen. Er findet es, zum Beispiel, faszinierend zu sehen, wie unterschiedlich Menschen altern. Welche genetische Disposition, fragt er sich, haben Menschen, die mit 80 immer noch Tennis spielen? Und weshalb können andere in diesem Alter kaum noch gehen?

Unsere Zeit ist abgelaufen, Peter J. Richards muss weiter, das nächste Meeting steht an. Wie sagte er gerade eben? „My brain has to be busy, that keeps me going.“

Portraitspeter j. richards

2928

His passion is his work: Peter J. Richards, sci-entific director of the CABMM and group leader of the Bone and Stem Cell Research Group. He can see parallels in his job as a research leader and as a father.

He arrives a little late, as his group meeting took a bit long-er. But then he is there, a tall man with blue eyes and with as much humor as passion for his research. His daily work? “Keeping an eye on what everyone is doing in the lab, com-ing up with new ideas, writing publications.” And organizing money for his research. This was something he had difficulties with in the beginning, as money doesn’t really mean that much to him personally. “For me, the important things are thinking and researching.”

peter j. richards, portrait by paula lanfranconi

“i see myself as a discoverer”

He came to this position from industry, where he worked on therapies for spinal injuries, but was never really satisfied doing only applied research. There were to many restrictions and not enough space for his own ideas, he says. “I see myself as a discoverer. I wake up in the morning with a new idea and say: maybe it’s a good idea, let’s try it out!”

Now as scientific leader of the CABMM, with all its different research areas, he can give valuable input based on his broad working knowledge in the areas of arthritis, osteoporosis and arteriosclerosis. His main focus within the CABMM is bone and stem cell research. His group tries to unravel the cellular mechanisms, which lead to osteoporosis of the bone. The ulti-mate goal is in the development of new treatment therapies. At the moment the treatment of choice is the application of bisphosphonates, although one potentially major side effect is the development of necrosis of the jaw after 10-15 years of treatment. Another highly effective therapy is the treatment with parathyroid hormone (PTH), a peptide hormone, which increases the generation of bone. But this treatment also has its drawbacks, as it can only be injected, although a PTH-nose spray may hopefully solve this.

“The major problem of osteoporotic bone is its fragility” explains the researcher, “possibly due to the increased pro-duction of fat tissue by resident stem cells at the expense of bone production.” His specialty: the team works with stem cells from fat tissue. There is a paradox: if you stimulate stem cells from fat tissue, they have the potential to form miner-alized tissue, “and in some cases, even more efficiently than bone stem cells themselves.” This is super – in vitro. The next step will be to implant these stem cells in vivo, with the hope that it may also work one day in humans. But there is still a long way to go.

Peter J. Richards is not just looking at osteoporosis from a research side. He explains that, “if I see elderly people on the street, then I sometimes think that this person might fall in a few years and suffer a fracture, possibly with a fatal outcome.” This is based on the fact that nearly a third of osteoporo-tic patients sustaining a fracture will die within the first year through complications such as pneumonia.

He himself has never had a fracture. His only accident, he describes amused, was when he fell from the sofa of his par-ents. “I was six and thought I was superman and so jumped”. He experienced how painful a fracture can be, when his little daughter Lucy broke her leg recently at the age of 4 whilst skiing. The first attempts were great fun but then she fell and screamed her head off. “Terrible for us parents!” The doctor did an X-ray and she had a typical ski boot fracture. Lucy got a cast which she enjoyed drawing on. After 5 weeks the bone was healed and the accident almost forgotten.

The researcher is amazed how much his daughters, Lucy 4 and Lisa 1, have changed his life. “Before”, he says, “it was just the lab and the work, from morning to night.” He does not come from a scientific background. His father was a pilot of the Royal Marines and his mother an Occupational therapist. When he was 7, the family moved back to England from Aus-tralia, where he was born. He was good in biology, did his PhD in immunology. But he was not yet satisfied and did postdocs in immunology and cell biology.

Love brought him to Switzerland in the end. He fell in love with a PhD student at the University of Wales. Her name was Sandra. She wanted to go back to Konstanz after her PhD, to be closer to her parents. So both young researchers found a position in Zurich, Peter J. Richards at the University Hospital of Zurich. There he worked already in the field of stem cells and osteoporosis.

For a long time, he considered himself not as a family per-son, but enjoyed much more to spend his free time on his surfboard. “But with little kids, priorities change: instead of surfing, one can go jogging and this also provides for a good mind-set”. Also going out to the cinema, which he loved doing before the kids arrived, is not really that important anymore.

When he comes home in the evening, the kids are happy to see him. “Most of the time at least.” Lucy the 4 year old tries to improve his German. In the beginning, it was difficult to man-age a family and a job at the same time. He works 150 % as scientific director, “I enjoy a certain amount of stress”. Often he has to work at home in the evenings on the computer. His wife, who works 60% sharing a position with another young mother, is sometimes not so pleased about this. “But” he says laughing, “I try not to let it take over.”

He sees parallels between his role as a father and as re-search leader. You are not really given any tuition in how to lead as a scientist, just as you are not really taught how to be a good parent.

Where does he see himself in 5 years? “Hopefully still in research“, he answers. And maybe he will be a professor by then. Although with his broad research fields it is not easy to find a topic for his habilitation. But to become a professor, would not be his only goal. He hopes to be able to publish more and to generate more money for the CABMM, which will allow it to expand into a large research centre.

He still has a lot of exciting questions to answer. He is fasci-nated in the different ways people can age. For instance, what is it that allows people at 80 years of age to still play tennis, while others of the same age can hardly move?

Our time is over. Peter J. Richards has to leave to the next meeting. And his final words? “My brain has to be busy, that keeps me going.”

Portraitspeter j. richards

3130

Eigentlich wäre sie gerne Medizinerin gewor-den, kann aber keine abgeschnittenen Finger sehen. So studierte Karin Würtz, 33, Pharmazie. Als Leiterin der Gruppe Wirbelsäulenforschung am CABMM hat sie immer die Anwendung im Blick.

Normalerweise fährt sie mit dem Mountainbike zur Ar-beit, auch im Winter. Die 15 Kilometer lange Strecke hat ihre Steilheiten, doch bis Karin Würtz ihr Rad schiebt, braucht es einiges. Diese morgendliche Anstrengung, sagt die zierliche blonde Frau jetzt in ihrem Labor an der Universität Zürich Irchel, bringe sie in die richtige Arbeitsstimmung: „Der Körper ist leicht ermüdet, der Kopf entspannt.“ Heute hat sie den Zug genommen. Sie trägt dezentes Make up, wollte frisch sein für den Fotografen.

Es ist früher Vormittag, die Stimmung im Labor locker. Eine Kollegin erzählt gerade von ihrem kleinen Sohn. Er ist drei, kennt bereits den Unterschied zwischen der Fellzeichnung eines Geparden und eines Tigers. Und natürlich sämtliche Automarken. Karin Würtz hört zu, lacht gerne und oft. Als Gruppenleiterin arbeitet sie häufiger am Computer als im Labor. Es gilt, die Übersicht über die verschiedenen Projek-te zu behalten. Viel Schreibtischarbeit fällt an - Beiträge für Kongresse, Meetings organisieren. Und Anträge schreiben, da-mit ihre Gruppe weiterforschen kann. Diese Anträge, sagt die junge Wissenschafterin, kämen ihr manchmal vor wie Babys: „Ich habe lange gebraucht, bis ich eine Ablehnung nicht mehr persönlich nahm.“

Ihre Gruppe forscht über Rückenschmerzen, eines der häu-figsten und kostenintensivsten Gesundheitsprobleme. Bei vie-len Kategorien von Rückenleiden, sagt Karin Würtz, kenne man die Ursache nicht und wisse oft auch nicht so richtig, wie man sie angehen solle. „Wenn Physiotherapie nicht hilft, kommen Schmerzmittel dazu und wenn auch das nicht hilft, wird häufig operiert.“ Doch Operieren sei kritisch, wenn man die Krank-heitsursache nicht genau kenne.

Das Forschungsteam gehört weltweit zu den wenigen, die sich mit bandscheibenbedingten Rückenschmerzen befassen.

karin würtz, portrait von paula lanfranconi

„man kann mich nur schwer aus der ruhe bringen“

Es ist ein schwierig zu beforschendes Gewe-be, weil es, zum Bei-spiel wie Knorpel, recht komplex aufgebaut ist. Primär untersucht die Gruppe, welche biologi-schen und molekularen Vorgänge in den er-krankten Bandscheiben ablaufen. „Ziel unserer Forschung“, sagt Karin Würtz, „ist letztlich, die Ursache der bandschei-benbedingten Rücken-schmerzen zu finden und neue Therapeutika zu entwickeln, welche die Schmerzentstehung auf der mole-kularen Ebene unterbrechen.“ Diese antientzündlichen Stoffe könnte man dann in die Bandscheibe spritzen und so Operati-onen verhindern oder zumindest hinaus zögern.

Die Gruppe arbeitet vor allem mit pflanzlichen Stoffen. Einer davon ist Resveratrol, ein Phytoalexin mit entzündungshem-menden Eigenschaften, welches zu den Polyphenolen gehört. Resveratrol, sagt Karin Würtz schmunzelnd, komme gut an, weil es vor allem im Rotwein enthalten sei, zu dem die meisten Leute eine positive Beziehung haben. Tests mit Ratten hätten sehr gute Resultate gebracht. Nun geht es darum, diese Tests auf ein grösseres Tiermodell auszuweiten und so zu optimie-ren, dass die Wirkung länger anhält.

Ein weiterer antientzündlicher Stoff, mit dem das Team arbeitet, ist Kurkumin, Gelbwurz. Der Gründer der Gruppe, erzählt Karin Würtz schmunzelnd, habe Kurkumin im Selbst-versucht getestet. Es sei in den Ferien in Frankreich gewesen, die ganze Familie war von Mücken zerstochen. Der Kollege habe auf dem lokalen Markt Gelbwurz gekauft, eine Paste zubereitet und die Familienmitglieder damit bestrichen. „Die-se Paste half viel effizienter als die bekannten Mittel aus der Apotheke.“

Karin Würtz bezeichnet sich als grossen Fan der angewand-ten medizinischen Forschung. Ihre Gruppe soll nicht ins Blaue hinaus forschen, um dann von den Klinikern zu hören: „Aber das funktioniert in der Praxis nicht!“ Am CABMM schätzt sie speziell die Translationalität, den engen Austausch mit unter-schiedlichen Forschungsdisziplinen – Molekularmedizinern, Biotechnologinnen, Experimentalchirurgen. Durch diese Zu-sammenarbeit und die netzwerkartige Struktur komme man auch leichter zu Forschungsgeldern.

Eigentlich hatte die gebürtige Oberbayerin Medizin studie-ren wollen. Sie gehöre aber, sagt sie, zu jenen Leuten, die keine abgeschnittenen Finger sehen können. So entschied sie sich für Pharmazie. Sie wollte „etwas Angewandtes machen, aber auch Grundlagenforschung“. Ihre Promotion an der Universität Ulm galt der Bandscheibe. Beinahe wäre sie danach in den USA geblieben. Sie hatte dort an einem Kongress eine Stelle ange-boten bekommen, „per Handschlag“. Nach zwei Jahren habe es sie jedoch zurück ins deutschsprachige Europa gezogen. Zur Wahl seien die Charité in Berlin und Zürich gestanden. „Ich entschied mich“, sagt sie, „für das CABMM, weil ich hier über die Bandscheibe weiterarbeiten kann.“

Die erste Zeit an der Limmat, bekennt sie, sei ein Kultur-schock gewesen. „Ich fühlte mich bereits sehr amerikanisch und hatte Mühe mit der reservierten schweizerischen Art.“ Inzwischen schätze sie die Ehrlichkeit und Zuverlässigkeit der Schweizer, die Sicherheit auch. Und die Natur sei „super“, rühmt sie. Sie treibt viel Sport: Biken, wandern, laufen. Im Mo-

ment trainiert sie für ihren ersten Halbmarathon. Da, sagt sie, sei sie ähnlich wie im Job: Wenn sie sich etwas vorgenommen habe, ziehe sie es durch, hole sich ihren täglichen Adrenalinkick am liebsten mit Leistung, „körperlich oder geistig.“

Eigene Erfahrungen mit Rückenverletzungen hat sie bisher nicht gemacht, „Gottseidank!“, sagt sie. Ein paar Wurzelstöcke auf dem Biketrail machen ihr durchaus Spass, halsbrecherisch stürze sie sich aber nicht die Berge runter : „Wenn man mal Einblicke in orthopädische Krankenhäuser hatte, weiss man, was so alles passieren kann.“ Manchmal, wenn sie aus dem Spitallabor eine besonders interessante Gewebeprobe einer Bandscheibe erhält, erfährt sie auch die Geschichte des ope-rierten Patienten.

Karin Würtz bezeichnet sich als neugierige Person. Sie möchte etwas Fassbares erreichen, findet es schön zu sehen, wie die eigene Arbeit fortschreitet und irgendwann ein Pro-dukt entsteht, das später vielleicht den Patienten helfen kann. Freude macht ihr auch ihr Team. Es ist jung, man habe viel Spass im Labor, verstehe sich auch privat gut. Eine ihrer Mitarbeiterin-nen, eine Doktorandin, ist bereits Mutter. Karin Würtz möchte in den nächsten fünf Jahren „wahrscheinlich ebenfalls Kinder.“ Und dann möglichst schnell zurück in den Beruf. Als Grup-penleiterin sei dies allerdings schwieriger : „Man braucht einen Partner, der bereit ist, die Kinder mitzubetreuen.“

Stress ist sich die junge Forscherin schon jetzt gewohnt, sie mag ihn sogar. „Man kann mich“, sagt sie, „nur schwer aus der Ruhe bringen. Es gelingt mir, vieles unter einen Hut zu brin-gen, ohne meine Persönlichkeit zu verändern und die Leute zu stressen, wenn etwas nicht klappt.“ Diese Lockerheit wird ihr künftig noch stärker zugute kommen. Innerhalb des nächsten Jahres möchte sie ihre Habilitationsschrift einreichen. Thema: Bandscheibenbedingte Rückenschmerzen – Ursachen und neue Therapieformen.

Sie hofft, dass das CABMM weiter wächst. Und dass es ihr gelingt, genug Drittmittel einzuwerben, um ihre eigene Stelle finanzieren zu können. „Es wäre schön“, sagt sie, „wenn die Karriereleiter langsam nach oben zeigt.“

Portraitskarin würtz

3332

Actually, she wanted to become a doctor, but cannot see any cut fingers. Thus, Karin Würtz, 33, studied pharmacy. As leader of the Spine Research Group at the CABMM, she keeps an eye on the clinical application of her research.

Usually, she rides by mountain bike to work, even in winter. The distance of 15 kilometres is sometimes rather hard going, but it would take a lot to make her get off and push her bicycle. This mornings exercise, says the dainty blond woman being now in her lab at the University of Zurich Irchel, takes her to the right working mood: “The body is slightly exhausted, the head clear.” Today, she took the train. She wears decent make-up, wanted to be fresh for the photographer.

It is early morning; the atmosphere in the lab is familiar. A co-worker tells her about her little son. He is three years old, knows already the different fur markings of a hunting-leopard and a tiger. And, of course, all auto brands. Karin Würtz listens, and often laughs. As a group leader, she works more often on the computer than in the lab. It is essential to keep an overview of the different projects. A lot of deskwork is incured – pub-lications for congresses, organization of meetings. And grant writing, so her group can continue its research. These grants, says the young scientist, sometimes appear to her like a baby: “It took me quite some time, until I didn’t take a rejection personally.”

Her group studies back pain, one of the most often occur-ring and most cost intensive health problems. “For a lot of cat-egories of back pain”, says Karin Würtz, “the cause is not yet known and it is also often unclear what should be done against it. If physiotherapy doesn’t do any good, pain medication will be given, and if this doesn’t help either, often surgery follows.” But surgery is critical, in particular if the cause of the disease is not exactly known.

The team is engaged in research related to disc-related back pain, a field of research in which very few groups worldwide are currently working on. It is a difficult tissue for research due to its complexity and is comparable in many ways to cartilage. Primary, the group investigates, which biological and molecu-

karin würtz, portrait by paula lanfranconi

“i am not so easily ruffled”

lar processes occur in the diseased disc. “The aim of our re-search”, says Karin Würtz, “ is to finally find the cause of disc-related back pain and to develop new therapeutics, which can interrupt the pain development on the molecular level.” These anti-inflammatory substances could be injected into the disc and thus, prevent surgery or at least delay it.

The group works mainly with herbal substances. One of them is resveratrol, a phytoalexin with anti-inflammatory prop-erties that belongs to the poly phenols. Resveratrol, says Karin Würtz with a smile, is very well received, because is it mainly contained in red wine to which most people have a positive relation. Experiments in rats showed very good results. Now, these experiments have to be extended to a large animal mod-el and optimized in such way that the effect is longer lasting.

Another investigated anti-inflammatory substance is cur-cumin, the main ingredient of curcuma. The founder of the group, explains Karin Würtz with a smile, tested curcumin on himself. He was on vacation in France; the whole family was bitten all over by mosquitoes. The colleague bought curcuma on the local market, prepared a paste and applied it to all fam-ily members. “This paste was much more efficient than all well known medications from the pharmacy.”

Karin Würtz describes herself as a big fan of applied medical research. Her group should not just shoot in the dark and then hear from the clinicians: “But this doesn’t work in practice!” At the CABMM, she particularly appreciates the translational approach, the close exchange with different disciplines in re-search – molecular medicine, biotechnology, experimental sur-gery. Thanks to this collaboration and the network structure, it would also be easier to get money for research.

Actually, the native Upper Bavarian wanted to study medi-cine. But she belongs, says she, to the kind of people who cannot see any cut fingers. Thus, she opted for pharmacy. She wanted “to do something applied, but also basic science”. Her doctoral thesis at the University of Ulm was about the in-tervertebral disc. Then she almost stayed in the US. She got a job offer at a congress, “by handshake”. But after two years, she wanted to go back to the German-speaking Europe. She had the choice between the Charité in Berlin and Zurich. “I decided”, says she, “for the CABMM, because here I could con-tinue working on the intervertebral disc.”

The first time at the Limmat, she admits, was a cultural shock. “I felt already very American and was struggling with the re-served Swiss manner.” In the meantime she appreciates the honesty and trustworthiness of the Swiss, the security as well. And the nature is “super”, she says with much praise. She does

a lot of sports: cycling, hiking, running. Currently, she trains for her first half marathon. Thereby, says she, it would be similar as at work: if she decided to do anything, she would go through with it, would take her daily adrenaline rush preferably by achievements “physically or intellectually”.

She hasn’t had any experiences of her own with back injury, as yet. “Thank god!” she says. Some roots on the biking trail would be definitely fun, but she wouldn’t throw herself down the mountains at breakneck speed: “If you’ve had some insight into orthopaedic hospitals, you know what could happen.” Sometimes, if she gets a particularly interesting tissue sample of an intervertebral disc from the hospital, she also learns about the history of the operated patient.

Karin Würtz describes herself as a curious person. She wants to achieve something measurable and likes to see the progress of her own work and how a product develops, which may help patients in the future. She also enjoys her team. It’s a young team, having fun in the lab and also getting along well in private life. One of her co-workers, a doctoral candidate, is already a mother. In the next five years, Karin Würtz would “probably also like to have children”. And then back to work as soon as possible. However, as a group leader this would be more difficult: “One needs a partner who would also be ready to care about the kids.”

The young researcher is already nowadays used to stress, she even likes it. “It is very difficult”, says she, “to get me ruffled. I am able to balance a lot of things without changing my per-sonality and stressing people if anything doesn’t work.” In the future, she will benefit even more from this relaxed attitude. Within the next year, she would like to submit her habilitation. Topic: Disc-related back pain – causes and new therapies.

She hopes that the CABMM will continue growing, and that she will be able to obtain enough third party funding to finance her own position. “It would be nice”, says she, “if the job ladder would slowly point upwards.”

Portraitskarin würtz

3534

There are a total of 7 research groups currently using the platform in total consisting of 19 people.

1. Bone & Stem Cell Research Group Group Leader: Peter J. Richards

2. Cranio-Maxillofacial Surgery and Implantology Group Group Leader: Brigitte v. Rechenberg

3. Equine Research Group Group Leader: Anton Fürst

4. Interventional Work Research Group Group Leaders: Daniel A. Rüfenacht, Brigitte v. Rechenberg

5. Musculoskeletal Research Unit Group Leader: Brigitte v. Rechenberg

6. Spine Research Group Group Leader: Karin Würtz

7. Tendon Repair Group Group Leaders: Anton Fürst (former group leader: Jörg Auer)

The members of these groups are working on a multitude of projects, which are introduced on the following pages.

We decided to present the research of one specific group in more detail in every yearly report and to give only a short overview about the others. This year, the scientific director of the CABMM Dr. Peter J. Richards takes the opportunity to describe the work of his group and to give insight into the background and the current treatment regimes in the field of osteoporosis.

research repor tscabmm research platform

research reportscabmm research platform

The CABMM Research Platform is a multidisciplinary organisation embedded within the Institute of Veterinary Biochemistry and Molecular Biology (IVBMB), University of Zurich. Our main objectives are to foster translational, clinically oriented research and to promote scientific collaborations be-tween CABMM members. The CABMM Research Platform is well equipped and provides a stimulat-ing environment, where basic scientists and clinicians can discuss their research and ideas and work shoulder to shoulder for the purpose of developing novel therapeutic approaches for the treatment of dysfunctional and diseased tissues.

34

3736

1. Bone & Stem Cell Research Group Group Leader : Peter J. Richards, PhD Group Members: Gregor Bahrenberg (PhD student), Stephan Glanz (PhD student), Marina Klawitter (research

assistant), Ali Mirsaidi (PhD student), Dr. André N. Tiaden (postdoc)

Osteoporosis is defined as a systemic dis-ease characterized by reduced bone mass and low bone mineral density, with a subsequent increase in bone fragility and vulnerability to fractures.

Bone is constantly being remodeled by a process called bone turnover, which consists of resporption of existing, old bone and its subsequent replacement by new bone. In the healthy organism, this process allows the regulation bone sta-bility as well as adaptation to changing environmental condi-tions, e.g. an increase in weight or sportive activities. Addition-ally, small tears or fractions can be directly repaired during bone remodeling.

The most frequent form of osteoporosis is post-meno-pausal osteoporosis (type I osteoporosis), which is character-ized as high turnover remodelling in comparison to the low turnover remodelling observed in senile osteoporosis (type II osteoporosis). The disequilibrium of the remodelling param-eters has the potential to cause deficits in the mechanical strength of bone resulting in an increased risk of fracture. The total number of fractures, and hence the cost to society, will increase dramatically over the next 40 years as a result of demographic changes in the number of elderly people. It has been estimated that by 2010, 12 million people over the age of 50 in the USA will have osteoporosis and a further two mil-lion cases are expected by 2020. As many as one in five peo-ple with osteoporosis die within the first year after sustaining a hip fracture and almost one third require placement in a nursing home following hospital discharge. Statistics for Swit-zerland alone estimated the direct medical costs related to hospitalization of osteoporotic patients in 2000 as being more than 350 million CHF. As such, osteoporosis is now regarded

osteoporosis

as being a major health problem and represents a significant economical burden.

The steady turnover of bone is directed through the con-trasting actions of bone-forming cells (osteoblasts) and bone-resorbing cells (osteoclasts), and alterations in this homeo-static balance can lead to detrimental effects on bone quality as seen in osteoporotic patients. The availability of effective treatments to combat bone loss and subsequent fractures is still an unsatisfactorily solved problem today, despite the numerous pharmacological and non-pharmacological treat-ments currently in use.

Current treatment of osteoporosis

The most widely used approach to enhancing bone strength in osteoporosis is through the prevention of bone loss using various anti-resorpitive agents including bisphosphonates, es-trogen, calcitonin and selective estrogen-receptor modulators (SERMs). However, there is now a growing body of experi-mental evidence to suggest that improvements not only in

bone mass, but also in bone quality, maybe brought about through the use of anabolic agents. This has lead to a shift in the treatment regimes previously employed to combat bone loss, with emphasis now being placed on targeting osteoblast-dependent bone formation as opposed to osteoclast-de-pendent resorption. To date, the only approved anabolic com-pounds currently being available are two forms of parathyroid hormone (PTH), a hormone secreted by the thyroid gland. Both forms, PTH1-34 and PTH1-84, have protective roles on skeletal integrity through stimulation of bone formation.

However, the use of PTH over the current anti-resorpitive therapies has not been substantiated by the efficacy data and therefore suggests that, along with the high expense and ex-tended treatment period associated with PTH, alternative bone-forming therapies may be required. For this reason, new treatment strategies are now being developed to target the cell source from which the bone-forming osteoblasts arise, namely the bone marrow-derived mesenchymal stem cells (BMSCs).

Role of BMSCs

Being osteoblastic precursor cells, BMSCs have the ability to develop into active, bone-forming osteoblasts. They are regarded as being key components of the bone multicellular unit due to this potential for osteogenic differentiation and thus play a central role in the overall maintenance of bone quality. However, their general fitness appears to decline with donor age and passage number in culture as evidenced by in-creases in cellular ageing markers and an inability to maintain osteogenic potential under normal conditions and following exposure to stress.

Such observations have therefore led to speculation that deficiencies in resident BMSC differentiation may play a sig-nificant role in the development of age-related osteoporotic phenotypes. This is supported by the discovery that BMSCs isolated from aged osteoporotic patients have a higher pro-pensity towards fat formation (adipogenesis) than bone for-mation (osteogenesis) and therefore implies that the struc-

tural abnormalities associated with osteoporotic bone maybe as a consequence of inadequacies in bone cell differentiation. As such, it is imperative to have a full understanding of the mechanisms governing BMSC osteogenesis in order to de-sign effective therapeutic interventions to enhance and pos-sibly even normalize bone quality in osteoporotic individuals.

Research of the “Bone and Stem Cell Research Group”

To this end, one of our major research aims within the “Bone and Stem Cell Research Group” is to characterize the functional role played by BMSCs in the development of os-teoporotic bone through the use of molecular, biochemical and histological techniques.

As such, part of our work is focused on elucidating novel pathways involved in regulating osteogenic differentiation and how these may contribute to the onset and progres-sion of osteoporosis. We are currently utilizing stem cells iso-lated from both human patients and experimental models and have developed the necessary techniques with which to successfully harvest and expand cells from specific stem

research reportsleading article osteoporosis

Positive staining (red) of a novel protein involved in bone formation in osteogenic 3D-spheroids composed of adipose-derived stromal cells. – Färbung (rot) eines neuen, in den Knochenaufbau involvierten Proteins in osteogenen 3D-Spheroiden aus Stammzellen des Fettgewebes.

Mineralization of osteogenic 3D-spheroids composed of adipose-deri-ved stromal cells. – Mineralisierung von osteogenen 3D-Spheroiden herge-stellt aus Stammzellen des Fettgewebes.

3938

cell niches. A better understanding of how osteoporosis is regulated at the cellular level could lead to the development of more effective therapeutic strategies to treat age-related bone loss. Furthermore, the potential benefits of having identified new regulators of bone formation could easily be extended to other orthopaedic-related areas including frac-ture healing, where there exists a growing need for more effective inducers of bone regeneration, especially where bone healing is severely impaired as is the case with critical sized defect fractures and non-unions.

In an alternative approach, we have also extended these studies to investigate the possibility of using stem cells, other than those isolated from bone marrow, for the purposes of restoring bone quality. These studies have been focused predominantly on the use of stem cells harvested from fat tissue, termed adipose-derived stromal cells (ACSs). Our findings to date suggest that ASCs isolated from experi-mental models of osteoporosis maintain telomere length, show no signs of premature cellular senescence and retain a high capacity for osteogenic differentiation. Such observa-tions therefore support the notion of adipose tissue being a valuable source of osteoprogenitor cells and that the ability of such cells to proliferate and differentiate does not appear to be adversely affected by the age or osteoporotic status of the donor from which they were isolated. Therefore, we envisage that in the future, autologous stem cells isolated from fat tissue will come to represent an alternative bone-regenerative therapeutic strategy for the treatment of age-related osteoporosis.

research reportsleitartikel osteoporose

Micro-CT analysis of tibiae from control (A) and osteoporotic (B) mice. The amount of trabecular bone (brown) is significantly reduced in osteoporotic mice. – Mikro-CT-Analyse von Schienbeinen nicht-osteo-porotischer Kontrollmäuse (A) und osteoporotischer Mäuse (B). Die Menge an trabekulärem Knochen (braun) ist in osteoporotischen Mäusen deutlich geringer.

osteoporose

1. Bone & Stem Cell Research Group Gruppenleiter : Peter J. Richards, PhD Forschungsgruppe: Gregor Bahrenberg (PhD student), Stephan Glanz (PhD student), Marina Klawitter (research

assistant), Ali Mirsaidi (PhD student), Dr. André N. Tiaden (postdoc)

Osteoporose ist eine systemische Erkrankung des Knochens, welche durch eine geringe Kno-chensubstanz und niedrige Knochendichte ge- kennzeichnet ist. Betroffene Patienten sind daher anfälliger für Knochenbrüche.

Knochen unterliegen einem ständigen Auf- und Abbau. Die-ser sogenannte Knochenumbau hält im gesunden Organismus die Knochen stabil und erlaubt eine Anpassung an sich ändern-de Belastungsverhältnisse, beispielsweise bei verstärkter sport-licher Aktivität oder Gewichtszunahme. Auch können durch den Knochenumbau kleine Risse und Frakturen im Knochen direkt repariert werden.

Die sehr häufig auftretende postmenopausale Osteoporo-se (Typ I Osteoporose) ist im Gegensatz zur senilen Osteo-porose (Typ II Osteoporose, Altersosteoporose) durch eine sehr hohe Umbaurate charakterisiert. Ein Ungleichgewicht im Umbauprozess des Knochens kann dabei zu Defiziten in der mechanischen Festigkeit führen, was wiederum in einem hö-heren Risiko für Knochenbrüche resultiert.

Es ist zu erwarten, dass die Anzahl an Brüchen und die da-mit verbundenen Kosten für die Gesellschaft aufgrund des demographischen Wandels in den nächsten 40 Jahren noch dramatisch zunehmen werden. Schätzungen zufolge litten in den USA bereits im Jahr 2010 zwölf Millionen Patienten unter den Folgen der Osteoporose und diese Zahl wird sich bis ins Jahr 2020 um weitere zwei Millionen erhöhen. Einer von fünf Patienten mit einer diagnostizierten Osteoporose stirbt innerhalb eines Jahres nach dem Auftreten einer Hüftfraktur, und ein Drittel benötigt im Anschluss an die stationäre Heil-behandlung die Unterbringung in einem Pflegeheim. Alleine in der Schweiz betrugen die Kosten für das Gesundheitssys-

tem im Jahr 2000 mehr als 350 Millionen Franken. Aus die-sen Gründen zählt Osteoporose heute zu den wichtigsten Gesundheitsproblemen und stellt eine enorme ökonomische Belastung dar.

Am kontinuierlichen Knochenumbau sind zwei unterschied-liche Zellarten beteiligt: die Knochen-bildenden Osteoblasten und die Knochen-abbauenden Osteoklasten. Änderungen im Gleichgewicht dieses Umbauprozesses zu ungunsten des Kno-chenaufbaus führen zu einer Verschlechterung der Knochen-qualität, wie sie zum Beispiel in osteoporotischen Patienten vorkommt. Trotz zahlreicher pharmakologischer und nicht-pharmakologischer Ansätze sind bis zum heutigen Zeitpunkt die Behandlungsmöglichkeiten zur Prävention von Knochen-verlust und den damit einhergehenden Knochenbrüchen noch immer nicht befriedigend.

Aktuelle Behandlung von Osteoporose

Die am weitesten verbreitete Therapieform ist die Verab-reichung von verschiedenen anti-resorptiven Substanzen wie Bisphosphonaten, Östrogen, Calcitonin und selektiven Modu-latoren der Östrogen-Rezeptoren, welche den Knochenab-bau verringern. Allerdings gibt es inzwischen wissenschaftlich fundierte Hinweise darauf, dass auch mit Hilfe von anabolen Substanzen, die den Knochenaufbau fördern, nicht nur die Knochenmasse, sondern auch die Knochenqualität verbessert werden können. Diese Erkenntnis führte dazu, dass vermehrt auch der Osteoblasten-vermittelte Knochenaufbau im Kampf gegen den Knochenverlust in den Fokus der Forschung rückte. Bislang gibt es allerdings nur ein zugelassenes, anaboles Thera-peutikum: das von der Nebenschilddrüse sekretierte Hormon Parathormon (PTH) in Form von PTH1-34 oder PTH1-84. Diese stimulieren die Knochenbildung und schützt somit die Integrität des Knochens.

Allerdings zeigte die Anwendung von PTH keine nachhaltig verbesserte Wirkung im Vergleich zur anti-resorptiven Thera-pie und ist mit hohen Kosten sowie langen Behandlungszeit-räume verbunden, so dass immer noch alternative, Knochen-aufbauende Heilmethoden benötigt werden. Zur Zeit stehen

A

B

4140

Behandlungsstrategien im Mittelpunkt der wissenschaftlichen Forschung, welche sich auf den Ursprung der Knochen-aufbau-enden Osteoblasten beziehen, nämlich auf die mesenchymalen Stammzellen des Knochenmarks (bone marrow-derived stem cells, BMSCs).

Die Rolle von BMSCs

BMSCs sind Vorläuferzellen von Osteoblasten, besitzen also die Fähigkeit, sich zu ausgereiften, Knochen-bildenden Osteo-blasten zu entwickeln. Aufgrund dieses sogenannten osteoge-nen Potentials spielen sie eine Schlüsselrolle im Knochen und sind an der Aufrechterhaltung der Knochenqualität beteiligt. Allerdings scheint ihre generelle Fitness mit dem Patientenalter und der Dauer der Kultivierung im Labor abzunehmen, was durch einen Anstieg an zellulären Altersmerkmalen und einem Rückgang der Fähigkeit zur Knochenbildung unter normalen sowie Stressbedingungen beobachtet werden konnte. Diese Entdeckungen führten zu der Hypothese, dass fehlerhafte Ab-läufe in der Differenzierung von ansässigen BMSCs zu Osteo-blasten eine wichtige Rolle bei der Entstehung von altersbe-

dingter Osteoporose spielen könnten. Die Beobachtung, dass BMSCs von älteren, osteoporotischen Patienten die Entwick-lung in Richtung Fettgewebe (Adipogenese) gegenüber der Differenzierung zu Knochengewebe (Osteogenese) bevorzu-gen, unterstützt diese Annahme. Die strukturellen Abweichun-gen im osteoporotischen Knochen könnten somit die Folge einer unzureichenden Differenzierung von Vorläuferzellen zu Knochenzellen sein. Deshalb ist es zwingend erforderlich, die Mechanismen der Osteogenese von BMSCs zu verstehen, um effektive Behandlungsstrategien zur Verbesserung und mögli-cherweise sogar Normalisierung der Knochenqualität in Os-teoporose-Patienten zu entwickeln.

Forschung der „Bone and Stem Cell Research Group“

Eines der wichtigsten Ziele der „Bone and Stem Cell Re-search Group“ ist deshalb, die Funktionsweise von BMSCs in der Entwicklung von osteoporotischem Knochen zu verstehen und mittels molekularer, biochemischer und histologischer Techniken zu charakterisieren.

Ein Schwerpunkt unserer Forschung liegt dabei auf der Aufklärung neuer Signalwege, welche in die Regulation der osteogenen Differenzierung involviert sind, und wie diese zur Entstehung und dem Verlauf der Osteoporose beitra-gen könnten. Momentan arbeiten wir sowohl mit humanen Stammzellen als auch mit solchen aus tierischen Modellsyste-men und konnten alle notwendigen Techniken zur Isolierung und darauffolgenden Expansion von Zellen aus verschiede-nen Stammzell-Nischen erfolgreich etablieren. Ein besseres Verständnis der Regulation der Osteoporose auf zellulärer Ebene könnte dabei zur Entwicklung besserer Therapiemög-lichkeiten von altersbedingtem Knochenverlust beitragen. Zudem könnten mögliche Vorteile von neu identifizierten Regulatoren der Knochenbildung auch auf andere Gebiete der Orthopädie wie beispielsweise der Frakturheilung aus-gedehnt werden. Auch hier besteht ein wachsender Bedarf an effizienteren Mitteln zur Förderung der Knochenrege-neration, vor allem wenn eine Beeinträchtigung der Kno-chenheilung vorliegt. Dies ist zum Beispiel bei sehr grossen Knochendefekten mit einer kritischen Grösse („critical size defects“) und schlecht heilenden Frakturen (sogenannten „non-unions“) der Fall.

In einem alternativen Ansatz untersuchen wir, ob Stamm-zellen, die nicht aus dem Knochenmark stammen, ebenfalls für eine Wiederherstellung der Knochenqualität genutzt wer-den können. Der Fokus liegt dabei auf Stammzellen aus dem Fettgewebe (adipose-derived stem cells, ASCs). Bislang zeigen unsere Ergebnisse, dass ASCs aus dem Fettgewebe von os-teoporotischen Modellsystemen ihre Telemorlänge aufrecht-erhalten, keine Anzeichen von vorzeitiger zellulärer Alterung zeigen und auch ein hohes Potential für die Entwicklung zu Osteoblasten beibehalten. Diese Beobachtungen stützen die Annahme, dass Fettgewebe eine gute Quelle für Knochen-Vorläuferzellen darstellen könnte, zumal die Teilungs- und Differenzierungsfähigkeit dieser Zellen weder durch das Alter noch den osteoporotischen Status des Spenders negativ be-einflusst zu sein scheint. Aufgrund dieser Erkenntnisse ist es denkbar, dass in Zukunft körpereigene, aus dem Fettgewebe isolierte Stammzellen eine alternative Knochen-regenerative Therapiemöglichkeit zur Behandlung von altersbedingter Os-teoporose darstellen könnten.

Visualization of fracture healing through the immunohistochemical staining of novel bone-forming proteins (brown) in chondro-cyte lacunae at day 14 (A) and in sites of active bone regeneration at day 28 (B). – Visualisierung der Knochenregeneration durch immunohistochemische Färbung eines neuen, knochen-bildenden Proteins (braun) in Chond-rozyten-Lakunen an Tag 14 (A) und an Stellen aktiver Knochenregeneration an Tag 28 (B).

A B

research reportsleitartikel osteoporose

4342

2. Cranio-Maxillofacial Surgery and Implantology Group Group Leader : Prof. Dr. med. vet. Brigitte v. Rechenberg, Dipl. ECVS Group members: PD Dr. med. dent. Stefan Stübinger

For the integration, stability and preservation of a dental implant, the structures of the surrounding hard and soft tis-sues – namely the jawbone and the oral mucosa – are very important and their significance on the successful fixation of dental implants has been clinically and scientifically assessed in several pre-clinical situations. Yet, there are only few data identifying the influence and relevance of the surgical tech-nique, e.g. approach and applied instruments, on the overall outcome and success of dental implants. Increase of lost tis-sue volume using own bone and mucosa transplants is well established in daily clinical practice to extend the width of the jawbone and adjacent soft tissue.

However, surgical difficulties like the bone cutting technique and an increased patient morbidity represent major disadvan-tages. Another serious complication and risk factor for stable and sustainable integration of bone and soft tissue transplants as well as dental implants is that of bacterial infection.

The high affinity and adhesion of microorganisms to implant surfaces impede normal physiologic or mechanical cleaning by

means of saliva or oral hygiene. Subsequent bacterial coloni-zation and biofilm formation can lead to a tremendous loss of dental hard and soft tissue structures. Following this, the onset of severe inflammatory reactions is often inevitable. In addition, bone loss following osteoporosis or cancer treat-ment with bisphonsphonates causes severe problems in oral and maxillofacial surgery. Despite modern and state-of-the-art technologies, there are currently still no convincing and successful treatment options available for bisphosphonate-induced bone loss.

Our own clinical research could demonstrate that antimi-crobial soft tissue treatment by lasers can have a beneficial impact on the healing tendency of adjacent infected hard tis-sue. Laser light can help to control or even prevent the del-eterious effect of oral bacteria on teeth or dental implants on their surface.

Therefore our research is aimed at the analysis of the mu-tual interaction mechanisms at the surface of implanted bio-materials and vital tissues. This will help to understand normal, undisturbed or compromised healing and integration of bio-materials into the living human body. Focus is placed on the analysis of principle biological reactions that have a vital influ-ence of early inflammatory soft tissue reactions on adjacent bone. A second main topic deals with the development and evaluation of innovative treatment strategies for regeneration of lost tissue structures (bone, mucosa).

3. Equine Research Group Group Leader : Prof. Dr. med. vet. Anton Fürst, Dipl. ECVS Group members: Dr. med. vet. Michelle Jackson (PhD stu-

dent), Dr. med. vet. Jan Kümmerle (PhD student)

Orthopaedic injuries account for the majority of career-limiting diseases in horses used for athletic purposes ranging from pleasure riding to high-performance sport endeavours like jumping, racing, endurance or dressage competitions. The advances in equine orthopaedics and diagnostic imaging have improved our understanding of many orthopaedic injuries and, in most instances, allow for a very well defined diagnosis in terms of structural assessment of damaged musculoskel-etal tissue.

However, advances in therapeutic methods are unable to keep pace with improvements in diagnostics – this is especially true in equine orthopaedics. Successful outcome is commonly hindered by the slow regeneration or even incomplete repara-tion of mesenchymal tissues: for example, equine fracture pa-tients commonly suffer from delayed bony union, horses with subchondral cystic lesions show incomplete regeneration of the bony defect even after surgical debridement and horses with tendon injuries require a very long phase of convales-cence and still have a high risk of re-injury because of insuf-ficient and minor-quality repair tissue within the tendon.

Therefore, our group aims to study and develop regenera-tive methods to improve healing of injured musculoskeletal tissue in the horse. In the field of tendon healing, this involves monitoring of the process of differentiation of mesenchymal

research reportsoverview cabmm research platformoverview cabmm research platform

stem cells to tenocytes (tenogenic differenation). Once this process is more clearly understood, we aim to improve the conditions of the stem cell environment to achieve regenera-tion of tendon tissue after stem cell treatment of a tendon lesion. In the field of bone regeneration, we aim to study the effect of different external sources of growth factors and cy-tokines on the activity of bone-forming osteoblastic cells. A suitable growth factor or cytokine combination could enhance bony regeneration, e.g. after debridement of subchondral cystic lesions, especially if delivered via a suitable matrix or carrier system.

4544

4. Interventional Work Research Group Group Leaders: Prof. Dr. med. Daniel A. Rüfenacht, Prof. Dr. med. vet. Brigitte v. Rechenberg, Dipl. ECVS Group members: Dr. med. Zsolt Kulcsar, Dr. med. Ajit Sankar Mallik, PhD

A cerebral aneurysm is a bulge or ballooning of a blood vessel in the brain, and its formation represents the second major pathology affecting the arterial system after atheroscle-rosis. When harboring a cerebral aneurysm, the major risk is its rupture, which causes bleeding within the brain or more precisely, subarachnoid and eventually intra-cerebral hemor-rhage. One third of patients suffering from subarachnoid hem-orrhage will die within 24 hours before receiving adequate therapy, and an other third will be severely disabled because of bleeding consequences. It is therefore very important to seek for adequate treatment modalities with which un-rup-tured aneurysms can be repaired and ruptured ones can be treated with minimally invasive methods.

A common choice is endovascular treatment, a surgical procedure in which a catheter is inserted directly into the blood vessel. The endovascular treatment of brain aneurysms has evolved from balloons through detachable micro-coils and intracranial stents to arrive to the use of potentially more promising blood flow modulating endovascular prostheses. There is little known about the hemodynamic and biological effects of such flow diverters in in-vivo circumstances. There-fore, the aim of the Interventional Work Research Group is to evaluate new types of such endovascular prostheses designed for intracranial aneurysm treatment.

5. Musculoskeletal Research Unit Group Leader : Prof. Dr. med. vet. Brigitte v. Rechenberg,

Dipl ECVS Group members: Sabine Koch-Schneidemann, PhD, Dr. med. vet. Flurina Clement Frey, PhD, Francis Pusch, veterinary doctoral student, Dr. med. vet. Simon Pot, Dipl ACVO, ECVO

The main interest of the MSRU is related to musculoskel-etal diseases (bone, cartilage, tendon, spine) with focus on bone and cartilage research. Additionally, soft tissue research (cardiovascular, wound and tendon healing) is also carried out. The group is specialized on large animal experiments and his-tology including paraffin, cryo- and immunohistology as well as histology of non-decalcified bone samples. A special fea-ture of the MSRU is its goal to implement Good Laboratory Practice (GLP). Filing the application to Swissmedic as well as subsequent GLP inspection and certification by Swissmedic is expected by the end of 2012. Together with Good Manufac-turing Practice (GMP) established at the “Zentrum für Regen-erative Medizin (ZRM)”, human clinical trials performed under Good Clinical Practice (GCP) at the University Hospital and

the close collaboration of the involved institutions, the Univer-sity of Zurich will then be able to offer the complete quality chain for research and development of new therapeutics.

In the reporting period, the following research projects were performed by the MSRU on the CABMM research platform:

Chondrocyte migration in cartilageSabine Koch-Schneidemann, PhD

Cartilage is a flexible connective tissue found in many areas in the body like joints, the rib cage, the ear, the nose, interver-tebral discs and other parts. Unlike other connective tissues, cartilage does not contain any blood vessels and therefore, heals very slowly. In general, regeneration of adult cartilage is greatly impaired. Whereas children are still able to completely regenerate cartilage defects by differentiation of cells from the periochondrium to chondrocytes and subsequent forma-tion of new cartilage, adult cartilage is usually incompletely repaired by connective tissue cells/scar formation.

Own histological analysis suggests that migration of chon-drocytes or their precursor cells may occur even in adult car-tilage and may play a role in cartilage regeneration. Therefore, this project examines the migration, regeneration and repara-tive potential of cartilage cells in vitro.

Superparamagnetic iron oxide particle (SPIONs) for cartilage repairDr. med. vet. Flurina Clement Frey, PhD

Cartilage degeneration caused by chronic diseases like rheumatoid arthritis and osteoarthritis requires medical treat-ment over a long period of time. However, the long-term ap-plication of drugs is often discontinued due to negative side effects such as gastrointestinal ulcerations or toxic effects on kidney or liver. Drug administration directly into the joint re-duces these adverse reactions, but short drug persistence and inadequate drug concentrations in the joint cavity often limit the success of these therapies.

research reportsoverview cabmm research platform

4746

In this project, a long-term therapy using superparamag-netic iron oxide nanoparticles (SPIONs) is investigated. SPI-ONs are very small synthetic magnetic particles that can be functionalized by surface engineering for drug delivery. Due to their magnetic properties, SPIONs can be restrained at desired locations by magnetic forces, thereby increasing the drug residence time. In a first step, their cellular uptake into chrondocytes and other cell types as well as their degrada-tion will be investigated in detail. Subsequently, the coating procedure of the SPIONs will be optimized for their use as long-term drug release system.

Wound healingFrancis Pusch, veterinary doctoral student

To date, several treatment options to improve wound heal-ing are already available, but there is still no “gold standard” in wound healing and thus, products promoting wound healing are still a matter of research. In addition to an accelerated healing, the prevention of scars is a major issue. At locations such as joints with only a thin layer of skin, but a high me-chanical exposure, the formation of scar tissue can result in compromised mechanical properties and thus, compromised use. Furthermore, scars represent a cosmetic problem.

Several herbal preparations or compounds have been used for centuries to treat medical problems including wound healing and are currently enjoying a boom in popularity. However, often their effects still have to be proven scien-tifically for licensing and registration purposes. That is why in this project, the effects of a special preparation of a herbal combination product on wound healing and scar formation has been investigated.

Corneal wound healingDr. med. vet. Simon Pot, Dipl ACVO, ECVO

According to 2005 WHO data, up to 8 million people worldwide are affected with bilateral corneal blindness, which is the second leading cause of blindness after cataracts. The number of unilaterally affected people is even much higher. Corneal scar formation is one of the major causes of corneal blindness and therefore, the focus of intense research ac-tivities. Resection and subsequent reconstructive surgery of scarred corneal surface tissue are often necessary to restore vision in affected eyes. The prognosis for significant improve-ment of vision after ocular surface reconstruction is less than 50% in eyes with widespread ocular surface changes. There-fore, it is important to gain more knowledge regarding ante-rior corneal wound healing pathophysiology and to develop new surgical treatment modalities.

The aim of this project is to develop an artificial, tissue engineered corneal construct in vitro closely mimicking the structure and function of the corneal surface in the living or-ganism that could be used as both, an effective in vitro model system as well as an optically functional and viable transplant.

research reportsoverview cabmm research platform

4948

6. Spine Research Group Group Leader : Karin Würtz, PhD Group Members: Lilian Quero (PhD student)

Back pain is one of the most cost-intensive health prob-lems in the world, with an extremely high prevalence. One specific form of back pain is called discogenic back pain, which can arise under certain degenerative conditions of the intervertebral disc. Disc degeneration is a complex process, but a common feature is the accumulation of specific matrix degradation products (e.g. fragmentation products), although quality and quantity of degeneration products can differ in a group with a similar degree of degeneration.

Based on this observation, the overall interest of the Spine Research Group is to elucidate cellular mechanisms during disc degeneration that may underlie the development of dis-cogenic back pain; this knowledge could be used to develop novel treatment options. More specifically, one hypothesis of our research is that certain degradation products may in-crease the levels of proinflammatory cytokines, which can irritate nerves in the outer part of the disc, thus contribu-ting to pain development. Another hypothesis is that certain biodrugs can interfere in this proinflammatory cascade and can thus be used to treat discogenic back pain in a minimal invasive manner.

7. Tendon Repair Group Group Leaders: Prof. Dr. med. vet. Anton Fürst, Dipl ECVS (former group leader: Prof. Dr. med. vet. Dr. h. c. Jörg A. Auer, Dipl. ECVS/ACVS), Group Members: Dr. med. vet, Felix Theiss, Dipl. ECVS

(PhD student)

Tendon injuries are a common cause of lameness and was-tage in horses. The conventional and most widely spread the-rapy for inflammation or irritation of a tendon (tendonitis) in the horse involves administration of anti-inflammatory drugs and introduction of a controlled exercise program adjusted by regular ultrasonographic examinations. However, the healing process is very slow and results in the formation of scar tissue, which is functional inferior compared to normal tendon tissue. This has important consequences for the animal in terms of reduced performance and a substantial risk of re-injury.

The aim of our group is to develop cell-based treatment strategies to enhance tendon healing in the horse resulting in a shorter convalescence period and an improved quality of re-pair tissue, thereby reducing the risk of relapse. To evaluate this therapeutic concept, unanswered questions, like differentiation capacity of applied cells, mode of action and most suitable ap-plication format need to be addressed. In a first step, we aim to identify the most suitable cell source to produce tendon

tissue. Therefore, mesenchymal stem cells derived from bone marrow, adipocyte tissue and the umbilical cord as well as fetal cells will be evaluated morphologically and histologically regar-ding their potential to differentiate into tenocytes in a three-dimensional tendon model system. Subsequently, the regene-rative capacity of the four cell candidates will be investigated in vivo in an acute injury tendon regeneration model in mice. In the same animal model, different application forms, e.g. single cell injections and injections of micro-tissues, will be compared.

research reportsoverview cabmm research platform

5150

cabmmstart-up grants

The grants support novel projects within the musculo- skeletal research field, with emphasis being placed on proof of principle, potentially high risk studies that would not yet be supported by other more competitive funding agencies. It is expected that the findings generated from these initial studies should be sufficient to enable further applications to be submitted on a larger scale to other funding agencies. Ap-plication requirements include CABMM membership and an affiliation to a Swiss institution of the principal investigator. Under no circumstances can applications be considered that involve industrial partners or animal experimentation.

We offer the opportunity to apply twice a year for such preliminary studies. The applicants can receive a maximum amount of CHF 40’000.– over a period of one year.

The peer-review process of grant proposals involves ini-tial scientific screening by the CABMM Steering Committee followed by expert evaluation by the members of the Sci-entific Advisory Board (SAB). The evaluation criteria include amongst others, relevance to the objectives of the CABMM, originality of the problem(s) addressed and scientific and technical excellence of the proposal and the team.

At the end of the funding period, every project is discussed in line with a SAB Meeting, and the project outcome is pre-sented during the CABMM Symposium.

Since its conception in 2010, the CABMM start-up grant has funded a total of seven projects with an overall amount of CHF 220’000.–. A tabular summary of all funded projects can be found on the following page. In the future, a brief description of all funded projects within the respective re-porting period will be published in this chapter of the yearly report.

At the beginning of 2012, one of the first projects to be funded by the CABMM start-up grant was successfully pub-lished in the Journal of Biological Chemistry (J. Biol. Chem. 2012;287(25):21335-45. PubMed).

The CABMM start-up grant is a peer-reviewed funding program designed to support collabora-tions within the CABMM network and is enabled by the generous financial support of the Mäxi Foundation.

50

start-up grants

5352

summary cabmm start-up grants

Role of serine protease HtrA1 in spinal disc degeneration

Modulation of extracellular matrix proteins by serine protease HtrA1 and its influence on bone formation

Investigating the role of Toll-like receptor 2 in intervertebral disc degeneration and inflammation

Identification of tenocytic specific markers in the horse

N,N-dimethylacetamid for bone regeneration and inhibition of bone resorption

Effect of bisphosphonates on the differentation potential of mesenchymal stem cells isolated from osteoporotic patients

Functional analysis of non-coding RNA in osteoclastogenesis

Project Title

Dr. Peter J. Richards*, Dr. Karin Würtz

Dr. Peter J. Richards*, Prof. Dr. Michael Blauth

Dr. Karin Würtz*,Prof. Dr. Steffen Gay, Dr. Oliver Hausmann

Dr. Paolo Cinelli*,Dr. Peter J. Richards,Dr. Felix Theiss (Prof. Dr. Anton Fürst)

Prof. Dr. Franz E. Weber

Dr. Peter J. Richards*,Prof. Dr. Michael Blauth, Dr. Richard Lindtner (Prof. Dr. Michael Blauth)

Dr. Raffaella Santoro*,Prof. Dr. Dr. Michael O. Hottiger

Total amount

Applicant(s) Amount

01/2011 - 12/2011

09/2011 - 08/2012

10/2011 - 09/2012

11/2011 - 09/2012

01/2012 - 12/2012

01/2012 - 12/2012

03/2012 - 02/2013

Funding period

CHF 24’140.00

CHF 27’663.00

CHF 35’000.00

CHF 32’617.00

CHF 40’000.00

CHF 23’000.00

CHF 39’043.40

CHF 221’463.40

* Main applicant

start-up grants

5554

Facts & Figures

Starting with only a handful of members in the founding year, the CABMM gained acceptance and reputation in the field of interdisciplinary and translational research during the ensuing years. The number of members has increased from 16 in 2008 to more than 40 active members in 2011, and is still continuing to grow. Although most of the associated scientists come from numerous institutions in Zurich, we also exhibit affiliations with other Swiss facilities (Bern, Lausanne) and have CABMM members from other countries, e.g. from Austria.

Within the network of the CABMM there are numerous joint research projects. Although some were started only very recently, several projects have been successfully com-pleted and are representative of long-standing collabora-tions between individual groups within the CABMM. One of the most important instigators for such collaborations is the yearly Spring Seminar and Symposium of the CABMM where the presentations of new findings by scientists working within the CABMM allow for the fruitful exchange of scien-tific knowledge and ideas.

In order to promote scientific collaborations and exchange, the CABMM aims to create and con-tinuously strengthen a network of active member groups working together on interdisciplinary and translational research projects. The number and quality of those CABMM members as well as their collaborative research projects and scientific publications with affiliation to the CABMM reflect not only the activity within the CABMM network, but also show the success and quality of the CABMM.

The fact that a large and diverse number of CABMM-af-filiated research articles have been published over the last three years is another testament to the scientific strengths and networking capabilities of our CABMM members.

On the following pages, CABMM members are introduced with the assistance of short profiles, which we hope will bet-ter exemplify both, the range and diversity of research be-ing conducted within the CABMM. Furthermore, we provide tables detailing both CABMM-affiliated published articles in scientific journals and also scientific research projects per-formed within the CABMM.

facts & f igures

member profiles, joint research projects and publications

54

5756

Name: Blenn, ChristianDr. sc. Institution: Institute of Pharmacology and Toxicology, Vetsuisse Faculty, University of ZurichCABMM collaborators: Felix Althaus, Michael Hottiger

Name: Boos, AloisProf. Dr. med. vet. Institution: Institute of Veterinary Anatomy, Vetsuisse Faculty, University of ZurichCABMM collaborators: Annette Liesegang, Brigitte von Rechenberg

CABMM joint projects: 1, 14

General research interest: Poly(ADP-ribosyl)ation Cell death Autophagy Ca2+-signaling Oxidative stress Cellular pathology of chlamydia infection

General research interest: Musculoskeletal system, uterus and placenta as well as digestive system of the cow.

Name: Boos, NorbertProf. Dr. med. MBAInstitution: Prodorso, Centre for Spinal MedicineCABMM collaborators: Stephen Ferguson**, Alfredo Franco-Obrégon, Benjamin Gantenbein**, Steffen Gay, Oliver Hausmann,

Brigitte von Rechenberg, Karin WürtzCABMM joint projects: 18, 19, 22Publications with affiliation to the CABMM: 1, 2, 15, 16, 17, 22, 24, 26, 27, 29, 32

General research interest: Recent findings suggest that the expression of pro-in-flammatory cytokines by resident disc cells might con-tribute to disc degeneration and so-called discogenic back pain. Our research projects focus on the identifica-tion of the signaling cascades leading to pro-inflammato-ry cytokine expression in the intervertebral disc and its relation to back pain. Detailed knowledge of these sign-aling events may lead to new potential pharmaceutical targets to interrupt pain inducing cascades at their ori-gin and therefore, would allow for new minimal-invasive treatment options of symptomatic disc degeneration.

Name: Althaus, Felix R. Prof. Dr. med. vet. Institution: Institute of Pharmacology and Toxicology, Vetsuisse Faculty,University of ZurichGrants: SNF, Swiss MedicCABMM collaborators: Sascha Beneke, Christian Blenn, Ramiro Dip

Name: Beneke, SaschaPD Dr. rer. nat.Institution: Institute of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of ZurichCABMM collaborators: Felix Althaus

General research interest: Our research focuses on the function of enzymes of poly(ADP-ribose) (PAR) metabolism and their involve-ment in cell death signaling. The poly ADP-ribosylation system represents a target for experimental pharma-cotherapy in diabetes, cancer, stroke and inflammation.

General research interest:

Poly(ADP-ribosyl)ation DNA repair & genomic stability Aging Parkinson’s disease Cell death and Ca2+

Name: Blauth, MichaelProf. Dr. med.Institution: Department for Trauma Surgery, Medical University of InnsbruckGrants: CABMM, AOCABMM collaborators: Brigitte von Rechenberg, Peter RichardsCABMM joint projects: 7, 23

General research interest: We are mainly focused on elucidating the role played by mesenchymal stem cells in geriatric musculoskeletal diseases. As a clinical trauma surgery department we have direct access to human patient material, which is processed in our cell culture lab. Experimental data are linked to data obtained from clinical tests and patient interviews and collected in a cell data base. The stem cells are analyzed by state of the art visualizing tech-niques, namely electron- and confocal microscopy, as well as biochemical and histological methods.

member profiles (in alphabetical order)

for further information on cabmm joint research projects and publications please refer to the respective numbers in the tabular summaries on pages 70-72 and 74-77

** CABMM member since 2012 ** CABMM member since 2012

Facts & Figuresmember profiles

5958

Name: Franco-Obrégon, AlfredoPhDInstitution: Rehabilitation and Regenerative Strategies Group (RRSG), Space Biology, ETH ZurichGrants: Foundation Suisse de Recherche sur les Maladies Musculaires (FSRMM), European Space Agency, Swiss Health

Agency (BAG)CABMM collaborators: Norbert Boos, Oliver Hausmann, Ralph Müller, Karin Würtz, Marcy Zenobi-WongCABMM joint projects: 22

General research interest: Sarcopenia, the loss of skeletal muscle mass with advanced age, underlies many disorders inflicting the elderly such as diabetes, osteopenia, cardiovascular disease, degenerative joint disease and systemic catabolism while concomitantly reducing their resistance to infection and compromising their ability to overcome trauma. My principal research focus is the development of strategies designed at main-taining muscle mass in the elderly and those suffering from imposed immobilization. We also study the fundamental cel-lular mechanotransduction process that initiates the devel-opmental programs of our major mechanosensitive tissues.

Name: Fürst, Anton Prof. Dr. med. vet., ECVSInstitution: Equine Hospital, Vetsuisse Faculty, University of ZurichGrants: Stiftung Forschung für das Pferd, UZH ForschungskreditCABMM collaborators: Paolo Cinelli, Peter Kronen, Lee-Ann Laurent

Applegate, Annette Liesegang, Brigitte von Rechenberg, Peter Richards, Jess SnedekerCABMM joint projects: 11, 13, 30

Name: Gay, Steffen Prof. Dr. med.Institution: Center of Experimental Rheumatology, University Hospital ZurichGrants: FP7 Masterswitch, IMI BTCureCABMM collaborators: Norbert Boos,Oliver Hausmann, Michael Hottiger, Karin Würtz

CABMM joint projects: 18

General research interest: Our technical expertise and interests cover all fields of equine surgery. Currently, our research focuses mainly on equine orthopaedics, e.g. the treatment of arthritis, subchondral cystic lesions (SCLs) and ten-don injuries in the horse. After successful develop-ment of new treatment options in vitro, the clinical caseload offers direct future opportunities for their clinical application.

General research interest: The Center for Experimental Rheumatology Zurich is performing molecular research in the field of rheuma-toid arthritis (RA) and related autoimmune diseases. Thereby, we investigate key molecular and cellular events in RA, osteoarthritis and scleroderma. In partic-ular, our research focuses on the activation of the in-nate immune system in RA and on epigenetic changes leading to the stably activated phenotype of RA syno-vial fibroblasts such as DNA and histone methylation, histone and non-histone acetylation, and the expres-sion of microRNAs.

Name: Bürki, KurtProf. Dr. sc. nat.Institution: Institute of Laboratory Animal Science, Vetsuisse Faculty, University of ZurichCABMM collaborators: Brigitte von RechenbergPublications with affiliation to the

CABMM: 20

General research interest: Our institute provides support in laboratory animal housing, laboratory animal medicine, rodent microsur-gery and the generation of transgenic animal models. An internet-based intergrated Research Animal Track-ing System (iRATS) is provided for the documentation of animal housing and use. Research activities focus on animal welfare (rodents) and stem cell biology (embry-onic stem cells and induced pluripotent cells).

Name: Cinelli, PaoloPD Dr. sc. nat.Institution: Center for Clinical Research, Clinic for Trauma Surgery, University Hospital ZurichGrants: Forschungskredit UZH, CABMMCABMM collaborators: Anton Fürst,

Michael Hottiger, Peter Richards, Raffaella Santoro, Jess Snedeker, CABMM joint projects: 8,13Publications with affiliation to the CABMM: 19, 20

Name: Dip, RamiroPD Dr. med. vet. PhDInstitution: Novartis Animal Health, Inc., Basel and Institute of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of ZurichGrants: Stiftung Forschung für das Pferd, Forschungskredit Nachwuchsförderungs-

kommission der Universität ZürichCABMM collaborators: Felix Althaus, Colin SchwarzwaldCABMM joint projects: 2

General research interest: Our laboratory is mainly interested in the analysis of the molecular mechanisms involved in the regulation of pluri/multipotency and differentiation of embry-onic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs). We are especially interested in the use of these stem cells in bone regeneration.

General research interest: We are interested in elucidating mechanisms of inflam-matory down-regulation by the adenosine receptor A2A (transcriptional regulation, alteration of cytokine profiles, etc.). We currently investigate the molecular events triggered by adenosine on mast cells and how the interplay between the involved signaling pathways can be modulated in the course of an inflammatory reaction. In addition, we aim at clarifying physiopatho-logical role of adenosine signaling in equine recurrent airway obstruction (RAO).

** CABMM member since 2012 ** CABMM member since 2012

Facts & Figuresmember profiles

6160

Name: Hoerstrup , Simon P. Prof. Dr. med. Dr. rer. nat.Institution: Clinic for Cardiovascular Sur-gery, Division of Surgical Research and Swiss Center of Regenerative Medicine, University Hospital and University of ZurichGrants: 7th Framework Programme/European Commission, SNF, Schweizerische Herz-

stiftung, Zurich State Program Sonderförderung (HSM)CABMM collaborators: P. Kronen, B. von Rechenberg, D. RüfenachtCABMM joint projects: 9, 20, 27Publications with affiliation to the CABMM: 12, 30, 33

Name: Hofmann-Lehmann, Regina Prof. Dr. med. vet.Institution: Clinical Laboratory, Vetsuisse Faculty, University of ZurichGrants: SNF, Forschungskredit UZH, Stiftung für wissenschaftliche Forschung UZH, EGMASA, Bundesprogramm Chancengleichheit, Industrie

CABMM collaborators: Annette Liesegang, Brigitte von Rechenberg, Raffaella SantoroCABMM joint projects: 24

Name: Hottiger, Michael O. Prof. Dr. med. vet. Dr. phil. IIInstitution: Institute of Veterinary Biochemistry and Molecular Biology, University of ZurichGrants: SNF, Oncosuisse, Novartis, CABMM, Forschungskedit UZH CABMM collaborators: Christian Blenn,

Paolo Cinelli, Steffen Gay, Brigitte von Rechenberg, Peter Richards, Raffaella SantoroCABMM joint projects: 12

General research interest: The research expertise of Prof. Simon P. Hoerstrup lies in the fields of tissue engineering, cell based therapies and disease modelling.Tissue engineering: including tissue engineered blood vessels, heart valves as well as microscale strategies for myocardial regeneration. Cell Transplantation: developing cell-based implants based on the design of in vitro generated microtissues to im-prove myocardial functionality of the diseased heart. Disease Modelling: studying e.g. inflammatory processes that occur in the early development of arteriosclerosis.

General research interest: Our interest is in clinical research, mainly clinical infectiology and clinical pathology. We apply animal models in experimental studies to investigate host-pathogen interactions and immunoprophylaxis. Our group has developed molecular and serological diag-nostic tools for a variety of infectious diseases. We are particularly interested in retroviral infections, haemotropic mycoplasmas and vector-borne diseases of domestic and wild animals. Together with the clin-ics of small animal medicine, we recently established the clinical infectiology.

General research interest: Inflammation is the biological response of tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective attempt of the organism to remove the injurious stimuli and to initiate the healing process. My laboratory is interested in the molecular mechanisms that regulate inflammation. In particular, we investigate the regulation of inflammation by post-translational modifications of proteins. Our current work focuses on the activation and function of the enzymes that catalyze these protein modifications and the identification of their target proteins.

Name: Gerber, Christian Prof. Dr. med.Institution: Department of Orthopaedics, University Hospital Balgrist, ZurichGrants: SNFCABMM collaborators: Brigitte von RechenbergCABMM joint projects: 15, 32

Publications with affiliation to the CABMM: 25

General research interest: Our research focus is primarily on surgical reconstruc-tive procedures on the shoulder. In a series of research projects on a sheep shoulder model, our group inves-tigated over the last fifteen years the etiology, patho-physiology and novel treatment options for rotator cuff tears. Particular interest lies in the degeneration and retraction of the musculotendinous unit in chron-ic tendon tears. Novel treatment approaches include chemical anabolic stimulation, mechanical expansion of the musculotendinous unit and optimization of the surgical techniques.

Name: Hämmerle, Christoph Prof. Dr. med. dent.Institution: Center of Dental Medicine, Clinic of Fixed and Removable Prosthodontics and Dental Material Science, University of ZurichCABMM collaborators: André Studart,Stefan Stübinger, Franz Weber

Name: Hausmann, OliverPD Dr. med. Institution: Neurozentrum Zentralschweiz, Hirslanden Hospital St.Anna, LucerneGrants: CABMMCABMM collaborators: Norbert Boos,Alfredo Franco-Obrégon, Steffen Gay, Karin Würtz

CABMM joint projects: 18, 22

General research interest: Our focus is to develop and teach clinical concepts for the treatment of patients in need of hard and soft tissue regeneration and the placement of oral implants for rehabilitation with fixed dental reconstructions. Research areas include regeneration of bone and oral soft tissues (pre-clinical animal models as well as clini-cal trial in patients). We aim for the development of barrier membranes for guided bone regeneration, the application of growth factors and carriers for bone formation and the application of biomaterials for aug-mentation of soft tissues.

General research interest: I am working as a neurosurgeon at the Hirslanden Klinik St. Anna in Lucerne. The research is focused on degeneration of the spine as well as on spinal cord in-jury. I am collaborating with Dr. Würtz in the most re-cent past. After obtaining ethical approval for the col-lection of disc biopsies in 2010, I currently provide the Spine Research Group with surgical material, which will be used for investigations.

** CABMM member since 2012 ** CABMM member since 2012

Facts & Figuresmember profiles

6362

Name: Kronen, Peter W. Dr. med. vet., DVM, ECVAAInstitution: Musculoskeletal Research Unit, Vetsuisse Faculty, University of Zurich/Veterinary Anaesthesia Services International, WinterthurGrants: Numerous Industry Grants, KTI/CTI, 3R

CABMM collaborators: A. Fürst, S. Hoerstrup, P. Kircher, B. von Rechenberg, D. Rüfenacht, C. Schwarzwald, J. Snedeker, C. Spadavecchia**, D. Spreng, S. StübingerCABMM joint projects: 17, 27, 28

Name: Laurent-Applegate, Lee Ann Prof. Dr. med.Institution: Department of Musculoskeletal Medicine, Service of Plastic and Reconstruc-tive Surgery, Unit of Regenerative Therapy, University Hospital LausanneGrants: Foundation S.A.N.T.E, Foundation Family Sandoz, Foundation Flavie,

CTI/KTI, Orthopedic Hospital FoundationCABMM collaborators: Anton Fürst, Brigitte von Rechenberg, Jess SnedekerCABMM joint projects: 26, 30

Name: Liesegang, Annette Prof. Dr. med. vet., ECVCN, IVASInstitution: Institute of Animal Nutrition, Vetsuisse Faculty, University of ZurichCABMM collaborators: Alois Boos, Anton Fürst, Regina Hofmann-Lehmann, Brigitte von Rechenberg, Peter Richards, Raffaella Santoro

CABMM joint projects: 1, 5, 21, 24

General research interest: Improvement of anaesthetic techniques and meth-

ods in large experimental animals (rabbits, sheep, pigs, goats)

Pain diagnosis in behavioral schemes (pain scales), their comparison with neurophysiological parameters and clinical relevance

General research interest: We are interested in addressing clinical problems relat-ing to tissue repair based on the concept that unlike adult tissue, fetal tissue undergoes rapid healing with little inflammation and no scar tissue. As such, our lab-oratory has now established cell banks of progenitor cells harvested from a variety of tissue sources includ-ing human bone, cartilage, disc, muscle, tendon and skin, and these are being used to successfully develop cellular therapies and associated delivery systems for severely burned patients, acute and chronic wounds and for all other musculoskeletal tissues.

General research interest: Bone and mineral research Importance of physiological and nutritional influences

on bone resorption and formation in general species. Measurement of bone and cartilage markers and bone

mineral density (quantitative peripheral computertomogra-phy) in many species, also during growth, gestation and lactation.

Active Ca resorption in the intestine with Immunhisto-chemistry and Western blot.

Mechanisms of longitudinal growth regulation within growth plates in foals and lambs.

Hormones of Ca metabolism Osteoporosis

Name: Hübscher, UlrichProf. Dr. med. vet.Institution: Institute of Veterinary Biochemistry and Molecular Biology,University of Zurich (host institute of CABMM)Grants: SNF, Swiss Cancer League

Name: Keller, Emanuela Prof. Dr. med.Institution: Neurocritical Care Unit, Department of Neurosurgery, University Hospital ZurichGrants: Von Tobel Foundation, Theodor und Ida Herzog-Egli Foundation, EU-Grant Eurostars/Eureka

CABMM collaborators: Daniel Rüfenacht

Name: Kircher, Patrick R.Prof. Dr. med. vet. PhD, ECVDIInstitution: Division of Diagnostic ImagingVetsuisse Faculty, University of ZurichGrants: Albert-Heim StiftungCABMM collaborators: Peter Kronen, Brigitte von Rechenberg, Daniel RüfenachtCABMM joint projects: 14, 17, 27

General research interest: Regulation of DNA repair in animal and human cells, with particular focus on oxidative damages in con-nection with diseases (cancer, neurodegeneration) and aging.

General research interest: Development and application of new optical tech-

nologies to monitor cerebral hemodynamics and oxy-genation in patients at risk for ischemic brain damage (including theoretical and healthy volunteers studies)

Clinical studies to examine the inflammatory re-sponse in patients with subarachnoid hemorrhage

Application and studies on new neuroprotective treatment strategies, like hypothermia in patients with subarachnoid hemorrhages

General research interest: We are interested in the development of Functional Magnetic Resonance Imaging (fMRI), and MR Spectros-copy in animal patients and animal models. In general, the cross-sectional angiographic techniques are being optimized and utilized in the group. The Division shall serve as centre of expertise in ani-mal imaging for all affiliates of the CABMM.

** CABMM member since 2012 ** CABMM member since 2012

Facts & Figuresmember profiles

6564

Name: Richards, Peter J. PhDInstitution: Bone and Stem Cell Research Group, Cabmm, University of ZurichGrants: SNF, Forschungskredit UZH, Stiftung Osteoporose Schweiz, CABMM, Uniscientia Stiftung, NovartisCABMM collaborators: M. Blauth,

P. Cinelli, A. Fürst, B. Gantenbein**, J. Goldhahn, M. Hottiger, A. Liesegang, R. Müller, B. von Rechenberg, R. Santoro, J. Snedeker, A. Studart, K. Würtz, M. Zenobi-Wong

Name: Rüfenacht, Daniel A. Prof. Dr. med.Institution: IWR – Interventional Work Research, Neuroradiology, Swiss Neuro Institute SNI, Klinik Hirslanden, ZurichGrants: SNF, Cardiatis, research stent Balt, research stent Rapid Medical, research stent Antia, research liquid polymer Philips,

clinical research medical imaging, Klinik HirslandenCABMM collaborators: S. Ferguson**, S. Hoerstrup, E. Keller, P. Kircher, P. Kronen, R. Müller, B. von Rechenberg, S. StübingerCABMM joint projects: 20, 27

Name: Santoro, Raffaella PhDInstitution: Institute of Veterinary Biochemistry and Molecular Biology, University of ZurichGrants: SNF, Oncosuisse, Novartis, Swisslife, CABMMCABMM collaborators: Paolo Cinelli,

Regina Hofmann-Lehmann, Michael Hottiger, Annette Liesegang, Peter RichardsCABMM joint projects: 8, 12, 24

CABMM joint projects: 4, 7, 13, 23, 31Publications with affiliation to the CABMM: 6, 11, 23, 30

General research interest: We are interested in characterizing the functional role played by mesenchymal stem cells in the development of osteoporotic bone through the use of molecular, biochemical and histological techniques. We are cur-rently utilizing stem cells isolated from both human patients and experimental models and have developed the necessary techniques with which to successfully harvest and expand cells from specific stem cell niches.

General research interest: The IWR group is interested in understanding, imaging and visualization of neurological diseases and minimally invasive treatment options (imaging methods, devices and implants). Our work currently focuses on neuro-vascular wall pathologies, in particular on intracranial aneurysms. By replicating the biological findings on a computer model, we intend to understand the life cycle of aneurysms, to understand the impact of en-dovascular flow correction on blood and vessel wall and to improve methods of imaging and endovascular treatment options.

General research interest: Every cell contains the same genetic information, yet they differentiate into distinct tissues and organs. This property is mainly interpreted at the level of epigenet-ics and chromatin structure via non-coding RNAs and modifications at histones and DNA. We try to eluci-date epigenetic mechanisms that establish and main-tain cell identity. Our mission is to define chromatin and epigenetic regulators that contribute to cell dif-ferentiation processes like osteoclastogenesis, stem cell-neuronal precursor transition, neoplastic transfor-mation and metastasis.

Name: Meyer, Dominik ChristophPD Dr. med. Institution: Department of Orthopedics, Balgrist University Hospital, Zurich Grants: SNF CABMM collaborators: Brigitte von RechenbergCABMM joint projects: 15, 32

Publications with affiliation to the CABMM: 25

Name: Müller, Ralph Prof. Dr. sc.Institution: Institute for Biomechanics, ETH Zurich, Grants: EU, NIH, SNF, NFP, SystemsX.ch, KTI, ETHIIRACABMM collaborators: Alfredo Franco-Obrégon, Jörg Gold-

hahn, Brigitte von Rechenberg, Peter Richards, Daniel Rüfenacht, Jess Snedeker, Wendelin Stark, André StudartCABMM joint projects: 4

Name: von Rechenberg, BrigitteProf. Dr. med. vet., ECVSInstitution: Musculoskeletal Research Unit (MSRU), Vetsuisse Faculty, University of ZurichGrants: KTI, CABMM, Industry grants CABMM collaborators: M. Blauth, A. Boos, N. Boos, K. Bürki, A. Fürst, C. Gerber,

S. Hoerstrup, R. Hoffmann-Lehmann, M. Hottiger, P. Kircher, P. Kronen, L. Laurent-Applegate, A. Liesegang, D. Meyer, R. Müller, P. Richards, D. Rüfenacht, J. Snedeker, D. Spreng, W. Stark, S. Stübinger, K.Würtz, M. Zenobi-Wong

General research interest: Our research focuses on surgical reconstructive pro-cedures on soft tissues such as muscles, tendons, liga-ments and menisci in the shoulder and the knee. In a sheep shoulder model, our group has investigated for fifteen years the etiology, pathophysiology and novel treatment options for rotator cuff tears. On the knee, we primarily investigate novel treatment approaches for the reconstruction and repair of the cruciate liga-ment in vivo and in vitro.

General research interest: We are interested in characterizing the material prop-erties of musculoskeletal tissues, the quantification of their adaptation from birth to death, with disease, and due to mechanical demands, as well as comparing the kinetics and kinematics of functional and dysfunctional systems. For this purpose, we develop, refine and use biomechanical engineering tools and concepts to ex-plore and understand musculoskeletal organisation, while maintaining a philosophy of respect and compas-sion for all human and animal life.

CABMM joint projects: 5, 9, 10, 11, 14, 15, 16, 17, 20 , 21, 24, 26, 29, 32Publications with affiliation to the CABMM: 5, 11, 13, 14, 21, 25

General research interest: Our main interest is in musculoskeletal research focusing on bone and cartilage. We investigate fracture and defect healing with or without the application of biomaterials/biomimetics, the influence of inflammation in bone and cartilage healing as well as the importance of physiologi-cal remodeling of subchondral bone and cartilage.

** CABMM member since 2012 ** CABMM member since 2012

Facts & Figuresmember profiles

6766

Name: Stark, Wendelin J. Prof. Dr. PhD Institution: Functional Materials Laboratory, Institute for Chemical and Bioengineering, HCI E 107, ETH ZurichGrants: SNF, Commission for Technology and InnovationCABMM collaborators: Ralph Müller,

Brigitte von Rechenberg, Stefan Stübinger, Franz WeberCABMM joint projects: 25Publications with affiliation to the CABMM: 21

General research interest: We are interested in the development of bioresorb-able materials for reconstructive bone surgery, based on calcium phosphates (TCP) and their composites with degradable biocompatible polymers like PLGA. Such PLGA/TCP/collagen membranes are designed to induce bone regeneration and prevent scar tissue for-mation on the other side. The research is also focused on the improvement of antibacterial properties of the implants using silver containing TCP nanoparticles without influencing the bioactivity.

Name: Stübinger, Stefan PD Dr. med. dent.Institution: Cranio-Maxillofacial Surgery and Implantology Group, CABMM, Musculoskeletal Research Unit (MSRU), Vetsuisse Faculty, University of ZurichGrants: KTICABMM collaborators: C. Hämmerle,

P. Kronen, B. von Rechenberg, D. Rüfenacht, W. Stark, F.WeberCABMM joint projects: 6, 10, 16, 25, 29Publications with affiliation to the CABMM: 3, 4, 5, 7, 8, 9, 13, 14, 28

General research interest: Our research is aimed at the core points affecting the strong interaction mechanisms and mutual inter-ference at the interface of oral hard and soft tissue structures. Focus is placed on the analysis of principle pathways and reactions that have a vital influence of early inflammatory soft tissue reactions on adjacent bone. A second main topic deals with the development and evaluation of innovative treatment strategies for hard and soft tissue regeneration.

Name: Studart, André R. Prof. Dr. PhDInstitution: Complex Materials, Department of Materials, ETH ZurichGrants: SNF & IndustryCABMM collaborators: Christoph Hämmerle, Ralph Müller, Peter Richards

General research interest: Our research is focused on the design and assembly of new porous materials and functional capsules of po-tential use as scaffolds and drug release agents in regen-erative medicine. In the area of porous materials, we are interested in studying hierarchical porous architectures that can provide physical and chemical cues to accelerate regeneration in soft and hard tissues. In the area of func-tional capsules, we use microfluidic devices to develop smart, responsive capsules that could potentially be used for the controlled release of drugs and growth factors in the body upon different types of external stimuli.

Name: Schwarzwald, Colin C. Prof. Dr. med. vet. PhD, ACVIM, ECEIMInstitution: Equine Internal Medicine, Equine Department, Vetsuisse Faculty, University of ZurichGrants: CLINOMICS project, Vetsuisse Faculty Zurich, Forschungskredit UZH,

Stiftung Forschung für das Pferd, Wolfermann-Nägeli FoundationCABMM collaborators: Ramiro Dip, Peter KronenCABMM joint projects: 2

General research interest: Large animal and comparative cardiology, with em-phasis on echocardiography, cardiac electrophysiology, hemodynamic monitoring, cardiovascular pharmacol-ogy and cardiac biomarkers.Planning to expand activities to rodent echocardiog-raphy.

Name: Spreng, David Prof. Dr. med. vet., ECVS, ACVECCInstitution: Section of Small Animal Surgery, Vetsuisse Faculty, University of BernCABMM collaborators: Peter Kronen, Brigitte von Rechenberg

General research interest: Our Group is interested in the pathophysiology of partial cranial (anterior) cruciate ligament rupture in the dog. We are currently working on understanding the pathomechanism of NO induced apoptotic cell death and its consequences on potential healing ca-pacities of the ligament.

Name: Snedeker, Jess G. Prof. Dr. PhDInstitution: Department of Orthopedic Biomechanics, University of ZurichInstitute for Biomechanics, ETH ZurichGrants: SNF, Balgrist Foundation, Robert Mathys Foundation, Chinese Research Council (CRC)

CABMM collaborators: P. Cinelli, A. Fürst, P. Kronen, L. Laurent- Applegate, R. Müller, B. von Rechenberg, P. RichardsCABMM joint projects: 30Publications with affiliation to the CABMM: 12

General research interest: The Snedeker Laboratory expertise is in the devel-opment and application of novel functional imaging platforms to quantify and characterize cell-matrix me-chanical interactions. The laboratory specifically tar-gets hypotheses related to the influence that extracel-lular matrix composition (collagen type, proteoglycan content) and mechanics have on tendon cell and stem cell behaviour (proliferation, differentiation).

** CABMM member since 2012 ** CABMM member since 2012

Facts & Figuresmember profiles

6968

Name: Auer, Jörg A. Prof. em. Dr. med. vet. Dr. h. c., ECVS, ACVSInstitution: Equine Hospital, Vetsuisse Faculty, University of Zurich

honorary members:

Name: Braun, Ueli Prof. Dr. med. vet. Dr. h. c.Institution: Department of Farm Animals, Vetsuisse Faculty, University of Zurich

Name: Goldhahn, Jörg PD Dr. med.Institution: Novartis Insitutes for Biomedical Research, Basel

alumni members:

Name: Weber, Franz E. Prof. Dr. rer. nat.Institution: Division of Cranio-Maxillofacial and Oral Surgery, Oral Biotechnology & Bioengineering, University Hospital ZurichGrants: SNF, EU-FP7, ITI, AO-CMF grantCABMM collaborators:

Christoph Hämmerle, Wendelin Stark, Stefan Stübinger, Karin Würtz, Marcy Zenobi-WongCABMM joint projects: 6

Name: Würtz, Karin PhDInstitution: Spine Research Group, CABMM, University of Zurich,D-HEST, ETH ZurichGrants: SNF, AOSpine, CABMMCABMM collaborators: N. Boos, A. Franco-Obrégon, B. Gantenbein**, S. Gay, O. Haus-

mann, B. von Rechenberg, P. Richards, F. Weber, M. Zenobi-WongCABMM joint projects: 3, 18, 19, 22, 31Publications with affiliation to the CABMM: 1, 2, 15, 16, 17, 18, 22, 24, 26, 27, 29, 31, 32

General research interest: The main interest of our research laboratory is the healing of large bone defects in the head region. To that end, we produce and design growth factors to promote bone formation and screen and character-ize small molecule enhancers for BMPs. We develop and test titanium based, natural and synthetic bone substitute materials and have a profound expertise on the development and design of biomimetic materials (fibrin gels, platelet rich plasma, synthetic hydrogels, synthetic fibrin, HA/TCP based materials) for in vitro and in vivo bone tissue engineering.

General research interest: We primarily aim to identify the mechanisms leading to degenerative disc disease by investigating biologi-cal, biochemical and molecular processes that typically occur in the tissue in case of painful degeneration. Fur-thermore, we use the obtained knowledge to develop and test (both in vitro and in vivo) more target-orien-tated, novel treatment options for patients with de-generative disc disease, such as minimal-invasive injec-tion of anti-inflammatory substances or non-invasive application of electromagnet fields.

Name: Zenobi-Wong, Marcy Prof. Dr. PhDInstitution: Institute for Biomedical Engineering, Laboratory of Biosensors and Bioelectronics, ETH ZurichGrants: SNF, FP7, AO foundationCABMM collaborators: Alfredo Franco-Obrégon,

Brigitte von Rechenberg, Peter Richards, Franz Weber, Karin Würtz

General research interest: We engineer 2D and 3D cellular systems mainly for cartilage repair applications. Natural and synthetic na-nofilms are used to coat tissues and cells, where the terminal layer and stiffness of the nanofilm controls cell adhesion and spreading. We are also using bio-printing techniques to pattern co-culture systems to study cell-cell and paracrine interactions. Other tools for developing functional mimics of the native 3D ex-tracellular environment include photocrosslinkable carbohydrate-based gels, incorporation of adhesion motives into gels and mechanical loading bioreactors.

** CABMM member since 2012

Facts & Figuresmember profiles

7170

joint research projects (in alphabetical order)

Absorption mechanisms in the intestines of goat and sheep

Adenosine signaling in recurrent airway obstruction-affected horses

Biological response of the intervertebral disc to repetitive short-term cyclic torsion

Characterization of bone turnover and remodeling in experimental mouse models

Development, implementation and validation of an osteopenic sheep model for use in evaluating novel implant fixation techniques in low density bone applications

Development of an animal model to study the osteonecrosis of the jaw

Effect of bisphosphonates on the differentiation potential of mesenchymal stem cells isolated from osteoporotic patients

Epigenetic rRNA gene silencing during ESC differentiation

Establishment of a cell- and tissue biobank

Evaluation of a new saw blade for atraumatic bone cutting

Evaluation of recombinant human bone morpho-genetic proteins (rhBMP-2) on equine osteoblasts and bone marrow-derived mesenchymal stem cells in vitro for a future clinical application in subchondrals cystic lesions (SCLs) in horses

Functional analysis of non-coding RNA in osteoclastogenesis

Identification of tenocytic specific markers in the horse

Impingement syndrome in hip joints

Improved cruciate ligament reconstruction through enhanced graft incorporation at the bone-graft interface – An experimental study in rabbits

Influence of different surface modifications and macro-designs of dental implants on the osseointegration

Intracranial tissue perfusion, pressure and temperature

Investigating the role of Toll-like receptor 2 in intervertebral disc degeneration and inflammation

Investigation of the novel treatment options for degenerative disc disease

In vitro point-of care blood clot profiling by thromboelastography

Local mechanisms in the growth plate of young growing animals

Mechanisms of mechanotransduction in human intervertebral disc cells upon stimulation with PEMF or strain

Modulation of extracellular matrix proteins by serine protease HtrA1 and its influence on bone formation

Monitoring osteomyelitis by biomarkers following systemic inflammation parameters

Number Number

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

Facts & Figuresjoint research projects

Title TitleCollaborator (CABMM members only)

Collaborator(CABMM members only)

Alois Boos, Annette Liesegang*

Ramiro Dip*, Colin Schwarzwald

Benjamin Gantenbein* / **, Karin Würtz

Ralph Müller*, Peter Richards

Annette Liesegang*, Brigitte von Rechenberg

Stefan Stübinger*, Franz Weber*

Michael Blauth, Peter Richards*

Paolo Cinelli, Raffaella Santoro*

Simon Hoerstrup*, Brigitte von Rechenberg

Brigitte von Rechenberg, Stefan Stübinger*

Anton Fürst*, Brigitte von Rechenberg

Michael Hottiger, Raffaella Santoro*

Paolo Cinelli*, Anton Fürst, Peter Richards

Alois Boos*, Patrick Kircher, Brigitte von Rechenberg

Christian Gerber*, Dominik Meyer, Brigitte von Rechenberg

Brigitte von Rechenberg, Stefan Stübinger*

Patrick Kircher, Peter Kronen*, Brigitte von Rechenberg

Norbert Boos, Stephen Ferguson **, Steffen Gay, Oliver Hausmann, Karin Würtz*

Norbert Boos, Karin Würtz*

Simon Hoerstrup, Brigitte von Rechenberg, Daniel Rüfenacht*

Annette Liesegang*, Brigitte von Rechenberg

Norbert Boos, Alfredo Franco-Obrégon*, Oliver Hausmann, Karin Würtz*

Michael Blauth, Peter Richards*

Regina Hofmann-Lehmann, Annette Liesegang*, Brigitte von Rechenberg, Raffaella Santoro

* Principal Investigator** CABMM member since 2012

* Principal Investigator** CABMM member since 2012

7372

New approaches for biomaterials-based soft tissue reconstruction

Osteochondral bone stimulation with fetal progenitor cells

Performance and safety of a new embolizing device in a pig model

Perioperative analgesic methods in experimental sheep

Photodynamic laser application for bisphospho-nate-induced avascular bone necrosis

Regeneration of equine weight bearing tendons

Role of serine protease HtrA1 in spinal disc degeneration

The effect of pharmacological and mechanical stimulation on the chronically retracted torn rotator cuff muscle – An experimental study in sheep

Number

25

26

27

28

29

30

31

32

Title Collaborator

Wendelin Stark, Stefan Stübinger*

Lee Ann Laurent-Applegate*, Brigitte von Rechenberg

Simon Hoerstrup, Patrick Kircher, Peter Kronen*, Daniel Rüfenacht

Peter Kronen*, Claudia Spadavecchia**

Brigitte von Rechenberg, Stefan Stübinger*

Anton Fürst*, Lee Ann Laurent-Applegate, Jess Snedeker

Peter Richards*, Karin Würtz

Christian Gerber*, Dominik Meyer, Brigitte von Rechenberg

* Principal Investigator** CABMM member since 2012

Facts & Figuresjoint research projects

7574

summary publications 2011 (order date of publication)

Kelm JM, Breitbach M, Fischer G, Odermatt B, Agarkova I, Fleischmann BK, Hoerstrup S3D Microtissue Formation of Undifferentiated Bone Marrow Mesenchymal Stem Cells Leads to Elevated Apoptosis.Tissue Eng Part A. 2011 Dec 13. (Epub ahead of print)

Weiler C, Lopez-Ramos M, Mayer HM, Korge A, Siepe CJ, Wuertz K, Weiler V, Boos N, Nerlich AG Histological evidence for intervertebral disc degeneration in lumbar surgical disc tissue samples suggests statistical association to increased Body mass index.BMC Res Notes. 2011 Nov 16;4(1):497

Chan SC, Ferguson SJ, Wuertz K, Gantenbein-Ritter BBiological response of the intervertebral disc to repetitive short-term cyclic torsion.Spine (Phila Pa 1976). 2011 Nov 15;36(24):2021-30

Brokopp CE, Schoenhauer R, Richards PJ, Bauer S, Lohmann C, Emmert MY, Weber B, Winnik S, Aikawa E, Graves K, Genoni M, Vogt P, Lüscher TF, Renner C, Hoerstrup SP, Matter CMFibroblast activation protein is induced by inflammation and degrades type I collagen in thin-cap fibroatheromataEur Heart J. 2011 Nov;32(21):2713-22

Wuertz K, Quero L, Sekiguchi M, Klawitter M, Nerlich A, Konno S, Kikuchi S, Boos NThe red wine polyphenol resveratrol shows promising potential for the treatment of nucleus pulposus-mediated pain in vitro and in vivo.Spine (Phila Pa 1976). 2011 Oct 1;36(21):E1373-84

Hauser-Gerspach I, Vadaszan J, Deronjic I, Gass C, Meyer J, Dard M, Waltimo T, Stübinger S, Mauth C. Influence of gaseous ozone in peri-implantitis: bactericidal efficacy and cellular response. An in vitro study using titanium and zirconia. Clin Oral Investig. 2011 DOI: 10.1007/s00784-011-0603-2

Weiler C, Schietzsch M, Kirchner T, Nerlich AG, Boos N, Wuertz K Age-related changes in human cervical, thoracal and lumbar intervertebral disc exhibit a strong intra-individual correlation.Eur Spine J. 2011 Aug 12

Klawitter M, Quero L, Bertolo A, Mehr M, Stoyanov J**, Nerlich AG, Klasen J, Aebli N, Boos N, Wuertz KHuman MMP28 expression is unresponsive to inflammatory stimuli and does not correlate to the grade of intervertebral disc degeneration.J Negat Results Biomed. 2011 Jul 29;10:9

Meyer DC, Gerber C, von Rechenberg B, Wirth SH, Farshad MAmplitude and strength of muscle contraction are reduced in experimental tears of the rotator cuff.Am J Sports Med. 2011 Jul;39(7):1456-61

Klawitter M, Quero L, Klasen J, Liebscher T, Nerlich A, Boos N, Wuertz KTriptolide exhibits anti-inflammatory, anti-catabolic as well as anabolic effects and suppresses TLR expression and MAPK activity in IL-1ß treated human intervertebral disc cells.Eur Spine J. 2011 Jul 26

Mirsaidi A, Kleinhans KN, Rimann M, Tiaden AN, Stauber M, Rudolph KL, Richards PJTelomere length, telomerase activity and ostegenic differentiation are maintained in adipose-derived stromal cells from senile osteoporotic SAMP6 miceJ Tissue Eng Reg Med; 28 June 2011

Franscini N, Wuertz K, Patocchi-Tenzer I, Durner R, Boos N, Graf-Hausner UDevelopment of a novel automated cell isolation, expansion, and characterization platform.J Lab Autom. 2011 Jun;16(3):204-13

Schneider OD, Mohn D, Fuhrer R, Klein K, Kämpf K, Nuss KM, Sidler M, Zlinszky K, von Rechenberg B, Stark WJBiocompatibility and Bone Formation of Flexible, Cotton Wool-like PLGA/Calcium Phosphate, Nanocomposites in SheepOpen Orthop J. 2011 Mar 16;5:63-71

Casanova EA, Shakhova O, Patel SS, Asner IN, Pelczar P, Weber FA, Graf U, Sommer L, Bürki K and Cinelli PPramel7 mediates LIF/STAT3 dependent self-renewal in embryonic stem cells. Stem Cells, 29(3): 474-485

Graf U, Casanova EA and Cinelli PThe role of the LIF-pathway in derivation and maintenance of murine pluripotent stem cells. Genes, 2011, 2, 280-297

Iatridis JC, Godburn K, Wuertz K, Alini M, Roughley PJRegion-dependent aggrecan degradation patterns in the rat intervertebral disc are affected by mechanical loading in vivo.Spine (Phila Pa 1976). 2011 Feb 1;36(3):203-9

Liebscher T, Haefeli M, Wuertz K, Nerlich AG, Boos NAge-related variation in cell density of human lumbar intervertebral disc.Spine (Phila Pa 1976). 2011 Jan 15;36(2):153-9 Quero L, Klawitter M, Nerlich AG, Leonardi M, Boos N, Wuertz KBupivacaine – the deadly friend of intervertebral disc cells?Spine J. 2011 Jan;11(1):46-53

Number Number

33

32

31

30

29

28

27

26

25

24

23

22

21

20

19

18

17

16

Facts & Figurespublications

** CABMM member since 2012

7776

summary publications 2010

Weiler C, Nerlich AG, Schaaf R, Bachmeier BE, Wuertz K, Boos NImmunohistochemical identification of notochordal markers in cells in the aging human lumbar intervertebral disc Eur Spine J. 2010 Oct;19(10):1761-70. Epub 2010 Apr 7

Stübinger S, Nuss K, Pongratz M, Price J, Sader R, Zeilhofer HF, von Rechenberg B Comparison of Er: YAG laser and piezoelectric osteotomy: An animal study in sheep Lasers Surg Med. 2010 Oct;42(8):743-51

Stübinger S, Biermeier K, Bächi B, Ferguson SJ, Sader R, von Rechenberg B Comparison of Er: YAG laser, piezoelectric, and drill osteotomy for dental implant site preparation: a biomechanical and histological analysis in sheep Lasers Surg Med. 2010 Sep;42(7):652-61

Kelm JM, Lorber V, Snedeker JG, Schmidt D, Broggini-Tenzer A, Weisstanner M, Odermatt B, Mol A, Zünd G, Hoerstrup SPA novel concept for scaffold-free vessel tissue engineering: self-assembly of microtissue building blocks J Biotechnol. 2010 Jul 1;148(1):46-55. Epub 2010 Mar 17

Egermann M, Heil P, Tami A, Ito K, Janicki P, Von Rechenberg B, Hofstetter W, Richards PJ Influence of defective bone marrow osteogenesis on fracture repair in an experimental model of senile osteoporosis J Orthop Res. 2010 Jun;28(6):798-804

Kelm JM, Fussenegger MScaffold-free cell delivery for use in regenerative medicine Adv Drug Deliv Rev. 2010 Jun 15;62(7-8):753-64

Stübinger S, Saldamli B, Landes CA, Sader RPalatal piezosurgical window osteotomy for maxillary sinus augmentation Int J Oral Maxillofac Surg. 2010 Jun;39(6):606-9

Stübinger SAdvances in bone surgery: the Er: YAG laser in oral surgery and implant dentistry. Clinical, Cosmetic and Investigational Dentistry 2010 Jun:2 47–62

Hauser-Gerspach I, Stübinger S, Meyer JBactericidal effects of different laser systems on bacteria adhered to dental implant surfaces: an in vitro study comparing zirconia with titanium Clin Oral Implants Res. 2010 Mar;21(3):277-83

Number

15

14

13

12

11

10

9

8

7

Richards PJ, Turner AS, Gisler SM, Kraft S, Nuss K, Mark S, Seim HB 3rd, Schense JReduction in postlaminectomy epidural adhesions in sheep using a fibrin sealant-based medicated adhesion barrier J Biomed Mater Res B Appl Biomater. 2010 Feb;92(2):439-46

Stübinger S, Nuss K, Sebesteny T, Saldamli B, Sader R, von Rechenberg B Erbium-doped yttrium aluminium garnet laser-assisted access osteotomy for maxillary sinus elevation: a human and animal cadaver study Photomed Laser Surg. 2010 Feb;28(1):39-44

Stubinger S, Etter C, Miskiewicz M, Homann F, Saldamli B, Wieland M, Sader RSurface alterations of polished and sandblasted and acid-etched titanium implants after Er:YAG, carbon dioxide, and diode laser irradiation Int J Oral Maxillofac Implants. 2010 Jan-Feb;25(1):104-11

Number

6

5

4

Stübinger SEr: YAG Laserosteotomie – eine Alternative in der Oralchirurgie zum Knochenschneiden: Was ist möglich und warum? Laserjournal 2009;4:20-23

Bachmeier BE, Nerlich A, Mittermaier N, Weiler C, Lumenta C, Wuertz K, Boos NMatrix metalloproteinase expression levels suggest distinct enzyme roles during lumbar disc herniation and degeneration Eur Spine J. 2009 Nov;18(11):1573-86. Epub 2009 May 23

Poveda L, Hottiger M, Boos N, Wuertz K Peroxynitrite induces gene expression in intervertebral disc cells Spine (Phila Pa 1976). 2009 May 15;34(11):1127-33

Number

summary publications 2009

3

2

1

Facts & Figurespublications

78

Jahresbericht 2010/2011des Centers for Applied Biotechnology and Molecular Medicine (CABMM)

ImpressumHerausgegeben vom Center for Applied Biotechnology and Molecular Medicine (CABMM),© alle Rechte vorbehalten

Verantwortlich für den Inhalt: S. Mark, M. Klawitter, P. Richards, B. von Rechenberg

Gestaltung: Jule Krüger Grafik Design, 8032 Zürich, www.designhexe.com

Druck: Kantonale Drucksachen- und Materialzentrale Zürich (KDMZ), 8090 ZürichOffsetdruck Goetz AG, 8954 Geroldswil

Korrespondenzadresse:Center for Applied Biotechnology and Molecular Medicine (CABMM)Universität ZürichFrau Dr. Silke MarkWinterthurerstrasse 1908057 Zürich