MSIF11 pp01-28 English - MS International Federation · The future for stem cell technology and MS This issue of MS in focus will discuss how advances in understanding stem cell biology

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MS in Focus Issue One • 2003

The Magazine of the Multiple Sclerosis International Federation

Issue One • 2002MS in focusIssue 11 • 2008

● Stem cells andRemyelination in MS

MSIF11 pp01-28 English.qxd 1/2/08 14:25 Page 1

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MS in focus Issue 11 • 2008

Editor and Project Leader Michele Messmer Uccelli,

MA, MSCS, Department of Social and Health

Research, Italian Multiple Sclerosis Society, Genoa,

Italy.

Executive Editor Melanie Hook, BA, PGDip,

Information and Communications Manager, Multiple

Sclerosis International Federation.

Editorial Assistant Chiara Provasi, MA, Project

Coordinator, Department of Social and Health

Services, Italian Multiple Sclerosis Society, Genoa, Italy.

International Medical and Scientific BoardReporting Member Chris Polman, MD, PhD,

Professor of Neurology, Free University Medical

Centre, Amsterdam, the Netherlands.

Editorial Board MembersNancy Holland, EdD, RN, MSCN, Vice President,

Clinical Programs, National Multiple Sclerosis Society,

USA.

Martha King, Director of Publications, National Multiple

Sclerosis Society, USA.

Elizabeth McDonald, MBBS, FAFRM, RACP, Medical

Director, The Nerve Centre, MS Australia (NSW/VIC).

Nicole Mulasits, Editor-in-chief of Neue Horizontemagazine, Austrian MS Society, Austria.

Izabela Czarnecka, President, Polish MS Society,

Poland.

Dorothea Pfohl, RN, BS, MSCN, MS Nurse, Clinical

Coordinator, Comprehensive MS Center of the

Department of Neurology at the University of

Pennsylvania Health System, USA.

Paul Van Asch, Director of Physiotherapy, National MS

Centre, Melsbroek, Belgium.

Nicki Ward-Abel, Lecturer Practitioner in MS,

University of Central England, Birmingham, UK.

We lead the global MS movement by

stimulating research into the understanding

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professionals and the international scientific

community.

Our objectives are to:

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Cover image: Coloured transmission electron micrograph (TEM)of a section through a stem cell. Illustration copyright © DRGOPAL MURTI / SCIENCE PHOTO LIBRARY

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Editorial Board


Stem cells: understanding their 4role in treating MS

Mesenchymal stem cells: promises 7and reality

Neural stem cells for myelin repair in MS 9

Human embryonic stem cells: an 12experimental and therapeutic resource?

Haematopoietic stem cell therapy: 16can we repair the immune system in MS?

Remyelination: the next treatment 18target for MS?

Building a policy on stem cells in MS 21

Your questions answered 23

Interview: Dr Pablo Villoslada 24

Stem cells online survey results 25

Reviews 26

Glossary 27


ContentsThere has been much controversy in the pressrecently about the pros and cons of stem cellresearch. Because the media plays such a prominentrole in conveying reports on current advances, thedebate about stem cells is often based on a lack ofaccurate and unbiased information.

Stories of miraculous recovery from MS are familiar to everyone. Stemcell therapies that are not exposed to scientific scrutiny and that preyon people’s often desperate search for a cure, are dangerous andunethical.

Research “news” presents us with prospects that require us to improveour understanding of the latest direction the research is guiding us into,with each fact demanding further examination and scrutiny.

This issue of MS in focus on stem cells and remyelination in MS comesat a time when the MS community is full of hope and purpose, andsome uncertainty as well. Understanding research involving stem cellsis complicated. In this issue of MS in focus we have brought togetherleading scientists who present a comprehensible picture of what isknown about stem cells at this time, and of where the efforts ofscientists around the world are focused. Our hope is that the content ofthis issue will provide readers with a better understanding of howprogress in research is bringing us closer to new therapeutic strategiesfor people with MS.

We hope this issue helps readers understand the immense effortinvolved in stem cell research, in terms of standards of excellence,scientific rigour, quality control, monitoring and reporting; standardsthat are indispensable if stem cell therapy is ever to become a realchoice for helping people with MS.

On behalf of the Editorial Board, I would like to thank Dr GianvitoMartino for his assistance in bringing together the authors of issue 11and for his help in ensuring that the content covers the most relevantissues in stem cell research in MS.

I look forward to receiving your comments.

Michele Messmer Uccelli, Editor

The next issue of MS in focus will be onSpasticity. Please send questions and lettersto [email protected] or marked for the attentionof Michele Messmer Uccelli at the Italian MSSociety, Via Operai 40, Genoa, Italy 16149.

Editorial statementThe content of MS in focus is based on professional knowledge and experience. The Editor and authors endeavourto provide relevant and up-to-date information. The views and opinions expressed may not be the views of MSIF.Information provided through MS in focus is not intended to substitute for advice, prescription or recommendationfrom a physician or other healthcare professional. For specific, personalised information, consult your healthcareprovider. MSIF does not approve, endorse or recommend specific products or services, but provides information toassist people in making their own decisions.

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Letter from the Editor

We have provided a glossary on page 27to help readers to understand this complex topic.



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Stem cells: understanding

Multiple sclerosis (MS) is most frequentlycharacterised by a relapsing remitting clinical coursein which the affected individual develops one ormore neurologic deficits which then resolve partiallyor completely over subsequent days or weeks.These relapses reflect the development of newlesions within the central nervous system (CNS) asvisualised by magnetic resonance imaging (MRI).Such lesions, when examined in the laboratory,feature inflammation, myelin destruction, and avariable extent of injury to the underlying axons.

A further concern is that the persistent absence ofmyelin contributes to the ongoing loss of axons,the apparent basis for the progressive nature ofMS in some cases. Persistent loss of myelin canmake axons more vulnerable to repeated injury,induce axons to make compensatory changes intheir properties (changes ion channel expression)that can result in further delayed insults to theaxon and remove the supportive factors requiredfor long-term axonal survival. This issue of MS infocus concentrates on whether stem cell treatmentcan repair or replace the damaged myelin as ameans to restore effective electrical conduction inthe CNS and thus result in the recovery ofneurologic function.

What are stem cells and what do they do?Stem cells, and certain types of “progenitor cells”,are classically defined as cells that are self-renewing (can divide and produce more ofthemselves) and that can differentiate into amature cell type with the properties of cells thatcomprise specific organs. The initial stem cells arethose which are the product of the first cell

divisions following ovum (egg) fertilisation, knownas conception. Such cells have the capacity todifferentiate into all the various cell types thatcomprise the body and are referred to aspluripotent stem cells.

During this process of differentiation, there are cellsthat still retain a capacity to self-renew but havemore restrictive potential regarding differentiation;for example, they are more limited as to what celltypes they may produce. The articles in this issuewill discuss specific stem cell types. Stem cells thatreside within the CNS and that can develop intoneural cells are referred to as neural stem orprogenitor cells. Some can produce all types ofneural cells whereas others appear to be morerestricted, including those that can only develop intomyelin-forming cells (myelin or oligodendrocyteprogenitor cells). Every cell in the body is createdwith specialised proteins, or receptors, and each cellhas a specific combination of receptors. Scientistshave used this biological uniqueness of stem cellreceptors to tag or mark cells. As discussed inindividual articles, these cell types can be identifiedby their expression of specific cell markers thatcorrelate with their state of maturation and/orexpression of gene products that regulate theirresponses to environmental signals.

Why might stem cells have a role in MS?Histologic and MRI studies both indicate thatremyelination can occur in MS lesions. The extentof such remyelination varies between lesions. Thereare a number of models of MS in animals in whichthe experimental demyelination induced by toxins orvirus/immune mechanisms is subsequently almostcompletely repaired. In these models the

Jack Antel, MD and Peter Darlington, PhD,

Montreal Neurological Institute & Hospital,

McGill University, Montreal, Quebec, Canada

Persistent loss of myelin can make axons more vulnerable to repeated injury.


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their role in treating MS remyelination is carried out not by the cells(oligodendrocytes) which initially made the myelinbut by immature progenitor cells or stem cells.These cells move to the site of injury (wheredemyelination has occurred) and develop intomyelin-producing cells. Such cells can be identifiedin various sites in the adult human CNS including inregions surrounding MS lesions.

What do we need to know about stem cells in MS?A central challenge for MS research is to definewhat limits the capacity of progenitor cells to repairthe lesions in MS. Considerations include:• numbers of progenitor cells available • whether the progenitors that are present are insome way defective

Stem cells have the capacity to differentiate into all the various cell types that comprise the body.


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• whether there are deficiencies in signals neededto recruit such cells to the lesions and to stimulatethem to mature into myelin-forming cells or,conversely, whether actual signals in the CNSenvironment inhibit such responses fromoccurring. Is repair limited by the extent ofdamage to the underlying axons?

A theme of this edition of MS in focus is to outlinethe approaches that are being used to understandthe make-up of progenitor or stem cells.

Translating stem cell biology into MSremyelination therapyThe current issue will present specific perspectiveson the biology and potential clinical therapeutic useof an array of stem cell populations. Stem cellpopulations that are not normally present in theCNS must be delivered to the CNS (exogenousrepair) and then induce them to directly participate

in the actual repair process. For stem cells residingwithin the CNS the potential exists to promoteendogenous (within the body) repair, for examplethe use of biologic or pharmaceutical agents thatcan cross the blood brain barrier to amplify cellnumbers and promote their development into usefulmyelin-producing cells.

The future for stem cell technology and MSThis issue of MS in focus will discuss howadvances in understanding stem cell biologycould lead us towards potentially using stem celltherapy for MS, specifically through combininginsights into the pathological features of MSlesions, therapies to control the immune-mediated injury phase of MS, and MRI todynamically monitor the MS disease process. Thestronger the foundation of knowledge, the morelikely it is that this “new biology” will translate intorational, safe and effective therapy.

The challenge of repairing the CNS in MS.

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Stem cells are heterogeneous cell populations,meaning they have various and differentproperties rather than being alike. They are oftenmistakenly considered capable of repairing almostevery tissue, because of their capacity todifferentiate into cells of every tissue type. Basedon these expectations, stem cells have beenproposed as a source of cells for tissue repair indifferent areas of regenerative medicine, includingneurology.

T and B cells are elements of the body’s immunesystem, also known as lymphocytes. Both types of

cells perform a role when the body is under attack:B cells produce antibodies and T cells mobiliseother cells as part of the immune response. In MSthe body orchestrates a faulty immune response.Autoreactive T and B cells in the CNS recognisethe body’s own myelin antigens as foreign bodies,attacking and destroying the myelin. Breakdownof myelin (demyelination) leads to impairment ofnerve conduction and, in the long run, neuronaldamage, the biological basis of irreversibledisability. The ideal treatment for MS shouldtherefore target the autoreactive cells, protect theassaulted CNS tissue and promote its repair.

Mesenchymal stem cells: promises and reality

Antonio Uccelli, MD, Neuroimmunology Unit, Department of Neurosciences,

Ophthalmology and Genetics, University of Genoa, Genoa, Italy


Fluorescent murine mesenchymal stem cells in culture transfected (modified) with a greenfluorescent protein.


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Recent studies conducted in experimentalautoimmune encephalomyelitis (EAE), the animaldisease that resembles MS, have demonstratedthat mesenchymal stem cells (MSCs) may be ableto achieve some of these goals.

MSCs were first characterised in the bonemarrow where they form cellular components inthe blood through closely interacting withhaematopoietic stem cells (HSCs). The naturalpathway of MSCs is differentiation towardtissues such as bone, joint, fat, muscle andtendons, referred to as mesodermal tissues.Based on their natural tendency, MSCs might bebetter considered as multipotent precursor cellsof mesodermal tissues, rather than true stemcells. However, under specific experimentalconditions, MSCs have the ability to differentiateinto other cell types including neural cells. Morerecently, studies have demonstrated that MSCscan affect many functions of cells of the immunesystem including activated T and B cells. In thepresence of MSCs, lymphocytes and otherimmune cells do not increase in number andcannot produce the inflammatory cytokines –signallers of the faulty immune attack. Based onthe capacity of MSCs to adjust the immuneresponse and their apparent ability todifferentiate into neural cells, MSCs were testedas treatment of EAE. Intravenous injection ofMSCs in mice with EAE led to a strikingimprovement in the clinical course of the diseaseand reduced inflammation and demyelination.This beneficial effect was obtained when themice were treated early after disease onset andwas associated with moderating the T and B cellresponse against myelin antigens detected inthe lymph nodes, suggesting the possibility thatMSCs may be able to modulate the autoimmuneattack against myelin. In contrast, clinicalimprovement was not seen in mice treated afterthe disease had reached the chronic phase.Injected MSCs could be detected inside theinflamed CNS, but without any significantevidence of them changing into neural cells.However, less axonal loss associated with anincreased number of neurons in the inflamed

areas of the CNS was observed. A protectiveeffect on neurons and other cell types exposedto inflammatory and other toxic threats has alsobeen demonstrated in a controlled environment(in vitro) and in animal experiments, suggestingthat MSCs could foster the survival of injured ordying cells in a living organism (in vivo).

As MS is a disease where neural degenerationfollows CNS inflammation and demyelination, theseresults suggest MSCs could be a potentialtreatment for MS. However, there is no evidence sofar that MSCs could become an effective therapyfor patients with severe disability due to chronic andirreversible neural loss. In this situation it is notknown whether MSCs, or any adult stem cell, couldregenerate the complex neural network needed torecover from severe impairment. Currentexperimental evidence indicates that this possibilityis, unfortunately, unlikely.

Despite these concerns, the use of MSCs for thetreatment of MS is possible and not some futuristicconcept. Indeed, MSCs have been obtained forclinical purposes through bone biopsy or throughaspirating fatty tissue. Although the long-termsafety of injected MSCs is still unknown, they havebeen used to foster the development of blood cells(haematopoiesis) upon bone marrowtransplantation from a non-compatible donor (adonor with a different blood type than the recipient)and as therapy for the treatment of a limitednumber of acute diseases including heart failureand graft-versus-host-disease (GVHD).

Thus, based on data from animals with EAE andclinical experience gained from other diseases,MSCs may represent a future therapy for thetreatment of people with rapidly worsening MS, inwhom currently available therapies are noteffective. Future studies must verify MSCs’capacity to differentiate into neural cells in vivoand possibly the promotion of endogenousrecovery by local neural precursor cells, whichsupport axons and produce the myelin sheath,thus providing hope for tissue repair andregeneration.


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What are neural stem cells?The very first indication of the existence of stemcells dates back to the end of the 19th century. Atthat time, scientists were able to hypothesise thatstem cells were present in both embryos and in theblood. Nevertheless, the notion that stem cells werepresent in the mature brain was neglected until theearly 1960s when new neurons generated from apopulation of dividing cells, thereafter named neuralstem/progenitor cells (NPCs), were first observed.Further studies conducted through the early 1980sdemonstrated that NPCs were self-renewing cellscapable of giving rise to a limited number ofmultipotent cell types in a laboratory environment,owing to their capability to alter into the three maincell types of the nervous system: neurons,astrocytes and oligodendrocytes.

Since the identification of NPCs, protocols aimed atobtaining large numbers of NPCs in vitro have beensuccessfully established. These harvestingprotocols support the concept that these cells mightrepresent a source of ready-to-use cells fortransplantation purposes in virtually any CNSdisorder including myelin disorders such as MS.

Neural stem cell therapy in MS – where arewe and where are we headed? Encouraging preliminary results have been obtainedby transplanting NPCs into rodents affected by EAE,

the experimental model of MS. However, there are stillsome issues we need to consider before any potentialapplication of such therapies in people with MS: • the ideal stem cell source for transplantation • the route of cell administration• the integration of the transplanted cells into thetargeted tissue.

Neural stem cellsfor myelin repair in MSGianvito Martino MD, Department of Neurology and Neurophysiology, San Raffaele

Scientific Institute, Milan, Italy

Neural progenitor cells might represent the idealcell source for cell-based therapies in myelindisorders.



Stem cell sourceBoth embryonic stem cells (ES) and NPCs mightrepresent the ideal cell source for cell-basedtherapies in myelin disorders. These cells areable to differentiate into myelin-forming cells andre-ensheath, in vivo, demyelinated nerves whentransplanted in animals with EAE. But each ofthese potential sources has complications.Ethical issues are not the only cause for concernsurrounding ES. Further studies have shown thatthe cells have a tendency to form tumours oncetransplanted. The use of NPCs is complicated bythe difficulty in obtaining these cells fortransplant to the person with MS withoutrejection. So far, the only available and reliablesource of NPCs is from a human foetus but thisrenders the transplantation procedure difficult

because the recipient would need chronicimmunosuppression, to avoid complicationscaused by the incompatibility between thedonor’s cells and the recipient’s cells.

Route of cell administrationThe route of cell administration representsanother key issue for stem cell transplantation.While direct cell transplantation into lesions canbe instrumental in CNS disorders characterisedby a single, well-identifiable area of damage,such as in Parkinson’s disease or a spinal cordinjury, alternative approaches have to beestablished in a disease like MS where multipleareas of damage are a typical feature. Multiplecell injections into the brain are unrealistic. Somerecent experiments have partially overcome this

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Since the identification of NPCs, protocols aimed at obtaining large numbers ofNPCs in vitro have been established.


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latter limitation. In animal models of MS, it hasbeen shown that NPCs may reach the mostareas of myelin damage when injectedintravenously (IV) or into the cerebrospinal fluid(IC) circulation.

Cell integrationThree steps are necessary to lead to apermanent restoration of nerve conduction.Transplanted NPCs should integrate into areas ofmyelin damage, differentiate into myelin-formingcells and re-ensheath the damaged nerves withnewly formed myelin. NPCs can differeniate intomyelin-forming cells once transplanted in vivo,but their capacity to reconstruct the actualcomplex brain architecture and to give rise toproperly operating cells capable of long-lastingfunctional integration into the brain circuits stillremains unproven.

On the other hand, recent data in animals withEAE suggests that NPCs may still be effectivevia therapeutic mechanisms. IV and IC injectionof NPCs has been shown to prevent myelindamage by exerting a potent anti-inflammatoryactivity leading to the death of the blood-borneinflammatory cells invading the CNS anddamaging the myelin sheath. This therapeuticeffect – which prevents secondaryneurodegeneration and irreversible neurologicalimpairment – does not rely on NPCs’ ability todifferentiate into myelin-forming cells. The effectis exerted mainly by NPCs that have notdifferentiated. Actually, the study showed thatless than 5-10 percent of the transplanted NPCsdifferentiated into myelin-forming cells in therodents with EAE that benefited from celltransplantation.

How scientists are using stem cells tounderstand MSSince NPCs residing in the adult brain areconsidered to be self-renewing, multipotent cellscapable of repairing brain lesions, it is not clearwhy such cells fail to promote stableremyelination in MS spontaneously over time.Preliminary experimental and human studies in

MS indicate that the inflammatory processleading to myelin damage might also causeselective damage to endogenous NPCs, or NPCsalready present in the organism itself. The moststriking evidence supporting this hypothesis isthat the vast majority of brain lesions irreversiblyprogressing in MS are located within theperiventricular area, the very same area whereNPCs accumulate during adulthood. Thus, NPCdamage can be, at least in part, responsible forthe failure of remyelination in people with MS.Understanding the interactions between cellsand how the interactions are regulated mightlead to therapeutic strategies aimed at re-establishing NPCs’ capacity to spontaneouslyregenerate in MS.

The future of stem cell researchBefore conducting small, phase I, safety trialsusing NPCs in MS, the scientific communitywould need to agree on important preliminariessuch as: • the establishment of common patientenrolment criteria and outcome measures (tocompare results, etc) • the establishment of a common registry oftransplanted patients• the development of reproducible and traceableprocedures for stem cell production (source ofthe cells, traceability of the donor, etc).

The future of this research also depends uponthe development of biomarkers, which aremolecules that allow for the detection andisolation of a particular cell type, and of MRItechniques aimed at assessing efficacy/toxicityof transplanted cells. Although it will take yearsbefore neural stem cell therapy will become aroutine therapy in MS, its safe and controlleddevelopment will certainly have a profoundimpact on the therapeutic options for thisdisease.

Safe and controlled development willhave a profound impact.


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The last decade has witnessed an unprecedentedexplosion of interest in stem cells in general andhuman embryonic stem (ES) cells in particular. It

has excited at turns both hope and fear in a widerange of groups, from the familiar stakeholdersthrough to policy makers and ethicists.

an experimental and therapeutic resource?

Human embryoSiddharthan Chandran, MRCP, PhD, Department of Clinical Neurosciences,

Centre for Brain Repair, University of Cambridge, Cambridge, UK

ES cells can generate a virtually unlimited supply of nerve cells (above) as an experimental anddrug discovery tool.



onic stem cells:ES – the ultimate repair kit?Most stem cells are restricted to making cellsthat belong to their tissue of origin. Forexample, nerve stem cells will make nerve cells.Human embryonic stem cells (ES) can make allthe cell types (over 200) that make up anindividual. The twin property of being self-renewing and pluripotent (unrestrictedspecialisation) means that ES may prove to bethe ultimate body repair kit.

Where are they from?ES are stem cells removed from embryos (fourto five days old) obtained from fertility clinics.These embryos were fertilised outside thebody (in vitro) and are donated for researchunder informed consent. The removed cells arethen grown on a layer of feeder cells in thepresence of specialised medium-containingnutrients (cell culture). Over time the ES willproliferate and out-grow the starting dish andbe reseeded onto several further dishes. Theprocess will eventually result in the generationof many millions of ES, all from just a fewstarting ES.

How can ES help scientists understand MS?MS treatments have two aims: to prevent and torepair damage. Despite important advances intreatments (disease-modifying medications)that reduce relapse rate and some emergingevidence that early treatment may limitdisability, no meaningful therapies are availableto prevent or repair fixed disability.

Therapy development requires an improvedunderstanding of the nature of disease

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Until the advent of ES the possibility ofwidespread study of human cells was simplynot possible.



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evolution and the failure of recovery. Currentlywe use many animal-based systems to learnabout MS. Although immensely valuable, thereremains a great need to be able to study humancells. Until the advent of ES the possibility ofwidespread study of human cells was simplynot possible.

An invaluable research resource for MSresearchers would be access to unlimitednumbers of human nerve cells andoligodendrocytes. ES make this feasible. Inorder to fulfil this possibility, scientists have firstto understand the process or signals that directan ES to become a nerve stem cell and then anerve cell or oligodendrocyte. Much researchfocuses on this and borrows heavily on insightsgained from studies of developing animals.Once understood, these chemical signals canbe applied under controlled conditions to driveES to become nerve stem cells, neurons oroligodendrocyte cells exclusively.

If unlimited numbers of human nerve andoligodendrocyte cells were available, importantquestions could be addressed. For example,knowing more about the chemical signalsbetween nerve cells and oligodendrocytes andhow this language is disrupted in MS. Suchknowledge may lead to therapies to restore thecorrect cellular dialogue in people with MS,thus promoting repair. The pharmaceuticalindustry is particularly interested in ES for thisreason. An ample supply of human cells wouldprovide a unique opportunity to test anddiscover new drugs.

Is there a role for cells made from ES tobe used in MS?It is incontrovertible that ES can generate avirtually unlimited supply of nerve cells as anexperimental and drug discovery tool. It is less

certain that ES have a role in cell-basedtherapies.

The damaged nervous system in people withMS can self-repair. Endogenous repair occurswhen oligodendrocyte cells lay down newinsulation around damaged nerves and thuseffectively provide a protective “plaster” knownas remyelination. Unfortunately in MS suchrepair is limited and inadequate. Stem cellscould enable remyelination by either acting as acellular reservoir of supportive factors that limitdamage and/or enable endogenousremyelination. In addition, stem cell-derivedcells, specifically oligodendrocytes, may beused to directly repair areas of injury. Animalmodels of MS support such an idea. However,given the fact that MS lesions can appear indiverse locations within the CNS, the method ofadministering such remyelinating cells hasbeen a conceptual obstacle. Recent findings doprovide some hope that intravenous delivery ofnerve stem cells will allow distribution of cellsto widespread areas of injury, an idea known as“homing”. However, there remain importantissues to be overcome before stem cells can beconsidered for clinical trial. These include thedevelopment of clinically compatible ES andmethods to ensure the exclusion of“contaminant” ES from “therapeutic” nerve stemcell preparations.

ConclusionThe science of ES is rapidly growing. Theprovision of unlimited numbers of humannerve cells for experimental study willaccelerate our understanding and thusdevelopment of new therapies for MS.Together this provides the basis for cautiousoptimism that meaningful therapies canemerge from ES.

Stem cells could enable remyelinationby acting as a cellular reservoir.

The method of administeringremyelinating cells has been aconceptual obstacle.


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Haematopoieticstem cell therapy:can we repair the immune system in MS?

Haematopoietic stem cells (HSCs) are the“seeds” of the cells that constitute our blood andimmune system. In adult humans, the home ofthese progenitor cells is the bone marrow, acomplex soft tissue that occupies hollow spacesinside bones, particularly large, flat bones.Throughout the span of our life, a large numberof HSCs continuously differentiate in order to fillup the blood and lymphoid organs with maturecells and replace the cells that reach the end oftheir useful life or are otherwise eliminated orlost. Thus, HSCs are essential for ourdevelopment and survival. In addition, HSCs’ability to repopulate the blood and immunesystem is an extremely useful property to treatcertain disorders. In fact, infusion of HSCs can“rescue” the subject from a failure of the bonemarrow that may result from marrow disorders orexposure to radiation therapy or chemotherapy,by generating a progeny of new healthy cells. Inexperiments, a single HSC has repopulated theblood of a mouse that received an otherwiselethal dose of nuclear radiation!

HSCs in the clinic: haematopoietic stemcell transplantationToday, haematologists routinely utilise HSCinfusion in a procedure called haematopoieticstem cell transplantation (HSCT) to promote the

recovery of blood cell numbers in people whoreceived high doses of immunosuppressiveradiation therapy or chemotherapy. Normally,HSCs are obtained either by direct aspiration ofthe bone marrow from the hip bones or throughmobilisation of the progenitor cells into theperipheral blood. Administration of a blood cellgrowth factor that stimulates production and the

Paolo A Muraro, MD, Department of

Cellular and Molecular Neuroscience,

Imperial College, London, UK

New and healthy immune cells from HSCs wouldbe “resetting the immunological clock”.


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release of stem cells induces HSCs to move outof the bone marrow and into the bloodstream.Blood is drawn from the patient into a cellseparator machine, which collects the mobilisedHSCs together with white cells in a processcalled leukapheresis. HSCs can subsequently bepurified by selecting cells bearing the markerCD34, which they specifically express on the cellmembrane. Umbilical cord blood is also rich inHSCs and has been utilised for haematopoietictransplants for cancer, particularly in children whodid not have a matching bone marrow donor. TheHSCs can be obtained from the same patientand preserved for re-infusion after thechemotherapy; this procedure is namedautologous haematopoietic stem celltransplantation (Fig. 1). Alternatively, a genetically“matching” donor can be identified among theperson’s relatives or through a bone marrow orcord blood donors’ registry; the transplantation of

HSCs from another individual is termedallogeneic transplantation. Allogeneic andautologous HSCT have different indications andboth are used extensively for treating cancers ofthe blood, of the lymphoid organs and of thebone marrow. Indeed, transplantation of HSCshas been a life-saving treatment for tens ofthousands of people affected by leukaemia,lymphoma, myeloma and other malignancies.

HCST for “immune repair” Clinical studies investigating the potentialusefulness of HSCT in MS and other immune-mediated disorders were initiated, following theobservation of those people with anautoimmune disease who, after developingcancer, were treated with HSCT andexperienced a remission of the autoimmunedisorder. These trials have been limited toautologous HSCT since allogeneic

Fig. 1 – HSCs can be obtained from the same individual and preserved for reinfusion.

Reprinted from LancetNeurology, Volume 4, Issue 1,Pages 54-63. Y Blanco, A.Saiz, E. Carreras, F. Graus,Copyright 2005, withpermission from Elsevier.


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transplantation has a higher risk of side-effectsand serious complications.

How does autologous HSCT work in MS?The lesions in MS are infiltrated by blood-originating immune cells including T and Blymphocytes that seem to attack and injuremyelin-producing cells. We do not know whatcauses this attack but the process almostcertainly involves a dysfunction of the immunesystem. The goal of HSCT in MS is to purgethe existing immune system withimmunosuppressive chemotherapy andregenerate a pool of new and healthy immunecells originating from HSCs. The idea hasbeen ingeniously termed as the “resetting ofthe immunological clock”. This means that inprinciple the mature cells of the immunesystem, and amongst them the cells thatattack the brain, can be eliminated andreplaced by new, harmless cells. Recentstudies have proven that this “resetting” of theimmune system actually occurs and that thethymus, the organ where haematopoieticprogenitor cells mature into T lymphocytes, isreactivated after HSCT giving rise to largenumbers of new T cells, possibly including“regulatory” T cells that suppress autoimmuneattacks.

What can HSCT do for people with MS?At the time of writing, more than 350 peoplewith MS have undergone autologoushaematopoietic stem cell transplantation.Although no randomised controlled studiesrigorously assessing the efficacy have yet beencompleted, an analysis of the reported resultsprovides some indication on what this treatmentcan and cannot do at the present time. Firstly,HSCT generally has shown beneficialsuppressive effects on inflammation anddevelopment of new plaques as detected byMRI. In the overall majority of treatedindividuals there was a stabilisation of the pre-existing neurological disability. Although inprinciple HSCs can transform into any celllineage, including neural or myelin-producing

cells, we do not know whether HSCs candirectly help repair the neural structures thathave already been damaged by MS. The clinicalstudies found that those who had a higher andchronically established degree of disability priorto HSCT frequently continued to worsen post-therapy. This observation suggests that thoseindividuals suffered from a type or stage ofneural deterioration that was not (or no longer)caused by the typical inflammation that HSCTcould not reverse or even arrest, in spite of itspowerful effects on the immune system.Therefore, clinical trials are now seeking torecruit earlier in the disease course, patientswith very active forms of MS who failed torespond to other immune treatments, in orderto determine if HSCT can prevent them fromworsening.

Current difficulties and hope throughresearchThe main difficulty in clinical studies of HSCTfor MS is the issue of treatment-related risks.Fatal complications have resulted from HSCTand while these occurrences have beendecreasing owing to improved knowledge andtechnology, life-threatening side-effects canstill occur. Another challenge is identifying earlythose who are affected by a severe form of MSand fail to respond to other treatments. It canbe reasonable to consider the option of anintensive therapeutic intervention for thesepeople, such as “immune repair” through HSCT.Treatment with HSCT should preferably bereceived through participation in a qualifiedclinical trial. Studies combining clinical andlaboratory research can help make HSCT saferand more effective and can teach us howchanges in the immune system can control thedevelopment and course of MS.

Studies combining clinical andlaboratory research can help makeHSCT safer and more effective.


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Remyelination,the next treatmenttarget for MS?

What is remyelination?The nervous system works because nerve fibres(axons) convey information between nerve cells(neurons) by way of electrical impulses. Theirability to do so is greatly enhanced by aninsulating sheath that wraps around the nervefibre. This sheath is made by a substance calledmyelin and in the CNS – the brain and spinalcord – myelin is made by a cell called theoligodendrocyte. In MS the oligodendrocyte andthe myelin sheath it makes are a major target ofthe disease process. Loss of oligodendrocytesleads to loss of myelin sheaths from aroundaxons – a process called demyelination. Theimmediate consequence of demyelination is thatthe axons become considerably less efficient atconducting impulses. However, demyelinationmay be followed by a spontaneous regenerativeor healing process in which new myelin sheathsare restored to the axons. This process is calledremyelination or myelin repair, although thisterm suggests that damaged myelin getspatched up – which is not really what happens –and enables the axons to resume efficientimpulse conduction.

Why is remyelination important?Remyelination is the normal response todemyelination and was first shown to occur inMS many years ago. More recent studies have

shown that in some patients, remyelination canbe very widespread and extensive. However, forreasons that are currently far from clear and arelikely to be multiple, remyelination is sometimesincomplete or fails altogether. This means thataxons remain permanently demyelinated; aserious situation since in this state they becomevery vulnerable to death themselves. A viewwidely held by MS researchers is that theprogressive loss of chronically demyelinatedaxons accounts for the progressive and largelyuntreatable deterioration experienced by nearlyall MS patients. Preventing axonal loss istherefore a major therapeutic objective which, itis hoped, will allow treatment of stages of thedisease for which none currently exist, and thatwill slow down or even arrest deterioration.Since myelin appears to be important formaintaining the health of the axons, manyexperts in the field believe that the therapeuticpromotion of remyelination in situations where ithas failed may represent one of the mosteffective ways of preventing axon loss.Preventing axonal loss is sometimes calledneuroprotection.

How might remyelination be enhanced?Since remyelination can occur as a spontaneousresponse to demyelination, one approach to itstherapeutic enhancement is to persuade the

Robin J.M. Franklin, Professor of Neuroscience and Director of the UK MS Society

Cambridge Centre for Myelin Repair, University of Cambridge, Cambridge, UK


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body’s own remyelination mechanisms not togive up but to work more effectively. This issometimes called the endogenous approach.Another approach is based on the argumentthat because endogenous healing has failed itneeds some external help, which can beprovided in the form of transplanted cells thatare able to make new myelin. This is sometimescalled the exogenous or cell therapy approachand is currently viewed by some as being moreappropriate for rare genetic diseases of myelinrather than MS. A third, combined approach alsoexists in which transplanted (exogenous) cellsare used to enhance endogenous remyelination.This approach is still in its infancy, but certainlyhas much potential. Recent experimentalevidence suggests the remarkable possibilitythat transplanted cells, easily delivered into theblood stream, not only encourage endogenousrepair but are especially effective at preventingdamage occurring in the first instance bydamping down the damaging inflammatoryresponse that characterises acute MS episodes(relapses).

An attraction of the endogenous approach isthat it may be amenable to drug-basedtreatments. In order for this to be developed it isnecessary to know why remyelination fails sothat the faulty aspects can be identified andcorrected. However, in order to do this it isimportant to understand how remyelinationworks. By analogy, it is very difficult to mend abroken car engine if you have nocomprehension of the engine’s internalworkings.

How does remyelination work? Remyelination is mediated by a population ofstem cells that are abundantly distributedthroughout the entire adult CNS. These cellsare often referred to as oligodendrocyteprecursor cells or OPCs. When demyelinationoccurs, all the OPCs in the vicinity are stirredinto action. This event is called activation andinvolves the cells increasing theirresponsiveness to factors generated by

demyelination that make them move aroundand make copies of themselves. Very quicklythe area of demyelination is filled up withOPCs, a process called recruitment. The nextstep is for these cells to become replacementoligodendrocytes that make new myelinsheaths around the demyelinated axons. Thisprocess is called differentiation. Thus,remyelination is the result of a two-stageprocess of OPC recruitment anddifferentiation. Over the last few yearsscientists have been busy identifying themultitude of factors involved in OPCrecruitment and differentiation. Some of theseare environmental factors to which the OPCsare exposed; others are factors within the

A section from the brain of a person with MS.Within the dark blue staining region (white matter)the pale (white) areas are demyelination - the paleblue areas are remyelination.


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OPCs that allow them to make the appropriateresponses to environmental factors. Whilemuch has been learnt it is apparent that thereis still a great deal more to be understood. Thenumber of factors is very large and most workin complex networks, making the process animmensely complicated one to understandcompletely.

Why does remyelination fail?In theory, remyelination might fail because of afailure of either OPC recruitment ordifferentiation, which would determine whetherremyelination therapies were to be based on theprovision of recruitment or differentiationfactors. Differentiation seems to be the morecomplicated of the two processes, and thereforethe one most likely to go wrong. It is thereforeof little surprise that recent evidence shows thata common cause of remyelination failure in MSpatients is not an absence of OPCs (these areoften present in abundance) but due to theOPCs failing to differentiate into remyelinatingoligodendrocytes.

At what stage is remyelination research? Because remyelination appears to be failing atthe differentiation stage, at least in aproportion of damaged areas in a proportion ofpatients, many scientists are currently focusingon how differentiation works and how it mightbe promoted. There are two possibleexplanations for differentiation failure andeither or both of which may be possible:differentiation may fail because of an absenceof factors to enhance it or the presence offactors that inhibit it. Several possibilities forboth explanations are being investigated.These studies usually take the form oflaboratory-based studies, using various animalmodels and cell cultures, and studies of post-mortem tissue from MS patients, which isbecoming increasingly widely available thanksto the setting up of specific MS brain banks.An excellent example is the one funded by theUK MS Society based at Imperial College inLondon. The results obtained from the twotypes of studies mutually inform each other –the post-mortem tissue pointing the way to thelaboratory studies and the laboratory studygiving clues as to what one might expect tofind in post-mortem material. This work isprogressing on many fronts via an increasingnumber of researchers and researchgroupings.

Although patient-based studies are currently inprogress to establish ways in which enhancedremyelination can be monitored and assessed inpatients, remyelination research is still at presentan essentially laboratory-based endeavour. Thisis inevitable considering the complexities of theproblem and it is worth remembering that thereare very few currently available treatments toenhance regenerative process for any tissue inthe body, let alone the CNS. Nevertheless,scientists and clinicians involved are optimisticthat in the future the availability of remyelinationtherapies will have a significant impact on thetreatment of MS, given the pace and momentumthat this important area of research has acquiredin recent years.

Adult stem precursor cells (above) give rise to newmyelinating cells in remyelination.


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In 2005, the Stem Cell Research Task Force ofthe National MS Society (USA) met with stemcell researchers, legal and regulatory experts,bioethicists, and other voluntary healthagencies. The task force found that researchwith all types of stem cells held great promise,potential, and hope for people affected by MS,and that there was a high likelihood that thisresearch would improve our understanding ofthe disease process and lead to new pathwaysfor therapeutic intervention. Membersrecommended that the Society be more publiclyactive to ensure that this research could move

forward. The Society approved therecommendations and asked chaptervolunteers and staff leadership to voiceconcerns, but little opposition was raised. “Wedid lose a few key volunteers whose counselwe valued highly by taking a more public profileon embryonic stem cell research, …however,we would not remain true to our mission if wecontinued to stay silent on this promising areaof research,” noted John R. Richert, MD,Executive Vice President of Research andClinical Programs of the National MS Society(USA).

Cathy Carlson, Senior Director, Research Information,

National MS Society (NMSS), USA

Building a policy onstem cells in MS

The task force found that researchwith all types of stem cells held greatpromise, potential, and hope forpeople affected by MS.

Programme cover from the Stem Cell ResearchSummit, convened by the National MS Society(NMSS) and the MS International Federation(MSIF) on January 16-19, 2007. It broughttogether leading stem cell and MS experts fromaround the world to explore the potential of alltypes of stem cells for the treatment, preventionand cure of MS.



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Among its recommendations were that theSociety should:• Continue to be open to funding stem cellresearch, including human embryonic stem cells.• Support somatic cell nuclear transfer(“therapeutic cloning”: implanting a person’sDNA into an unfertilised egg to grow stem cellsthat could be used to treat that person’s medicalcondition) for biomedical research, but opposeits use for reproductive purposes.• Publicly advocate for policies conducive toembryonic stem cell research, and clearlyarticulate the Society’s position.• Respect the beliefs of those who may opposethe Society’s stance, but not permit such beliefsto limit its research or advocacy activities.

• Establish an Ethical, Legal & SocialImplications Committee to review Societypolicies periodically and serve as a forum foraddressing public comments.• Sponsor a scientific workshop on stem cellresearch in MS.

Steps to consider in developing astem cell policy What steps might other MS societies take todevelop a stem cell policy? Here are a fewrecommendations, based on the NMSS’sexperience: • Cooperate with research centres in yourcountry, provide them with any support theyneed.• Know the political climate of your country interms of human embryonic stem cell research.• Through letters received or a survey,understand where the majority of yourconstituents and supporters stand on stem cellresearch (providing information about itspromise for people with MS may help pave theway for a positive response).• Consider steps you might take to propel thisresearch. Is it to advocate for policy changes, tojoin a coalition working for change, to fund stemcell research? For each of the possible steps,have your leadership weigh the possible risks(such as losing key supporters) and benefits(such as moving research forward for peoplewith MS).• Once you have arrived at a position, invest timein educating your constituents about the issueand communicating your position clearly andconsistently to them. • Let your mission drive your actions.

Details about Summit presentations can befound on the NMSS’s website:www.nationalMSsociety.org/stemcell

Recommendations from the National MS Society Stem CellResearch Task Force

John R. Richert, MD welcomed Stem CellSummit participants and asked for their help insetting research priorities.

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Your questions answeredDr Gianvito Martino answers questions

here based on evidence concerning

autologous haematopoietic stem cell

transplantation, the only type of stem

cell therapy currently available in people

with MS.

Q. Would I be able to choose which stemcells to use for ethical reasons?A. Presently, the only stem cell therapyavailable is that based on autologoushaematopoietic stem cell transplantation. Otherpossible stem cells (mesenchymal, neural, etc.)are still far from being used routinely in theclinic. Thus, at this time there is no possibility tochoose.

Q. Is stem cell therapy a “one-time”treatment or can it be an ongoingprogramme?A. So far autologous haematopoietic stem celltransplantation has been performed as a “one-time” treatment for patients with MS. It cannotbe excluded that in the future whatever type ofstem cell therapy used will require repeated ormultiple treatments.

Q. Would stem cells help me even if myMRI results show no new lesions?A. Currently there are no consistent datashowing that autologous haematopoietic stemcell transplantation can be effective when nosigns of ongoing inflammation are present. Onthe other hand, it appears that the moreinflammatory the disease, the better theoutcome after transplantation.

Q. Where do embryonic stem cells comefrom? Can they be created or must theycome from a living organism?

A. Presently, human embryonic stem cells(ES) come only from early stage humanembryos (those used for in vitro fertilisation) orfrom therapeutic cloning. In mice the possibilityof obtaining ES from mature cells (for exampleskin cells) is possible, thus avoiding the use of“living organisms”. Very recently it has beenshown that a procedure called “somatic cellprogramming” is also possible using humanadult tissues. In November 2007, ShinyaYamanaka of Kyoto University in Japanreported making pluripotent (ES-like) cells –cells that can turn into any of the roughly 220cell types in the body – by using retroviruses tocarry three key genes into human skin cells.Although this can be considered as a majoradvancement in ES research, it is a generalbelief that much more work needs to be donebefore translating such advances into clinicalpractice.



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Interview: Dr Pablo VillosladaCan you please tell us a bit about yourselfand your work?I am a neurologist working at the Multiple SclerosisCentre at the University of Navarra in Pamplona,Spain. I trained in Barcelona and San Francisco,California, and my focus has always been on MS. Atthe MS Centre we are trying to understand thepathogenesis of MS, including undertakingbiological studies to understand the disease andhope to use this information to find biomarkers andMS therapies.

Do many of your patients ask you aboutstem cell research and MS?More than 30 percent of my patients ask aboutstem cell therapy, especially those with a high levelof disability. More people ask now than they used todue to stories in the press of people having therapy,but there has always been an interest. Many peoplesee stem cells as a way to renew their body – a bitlike doing up a house – and are interested, even ifthey normally do not like the idea of taking drugs.

What questions do they ask?The main question they ask is: “What about stemcell therapy for me?”, but many are not aware of thescientific complexity of this subject. They have oftenread or heard about someone else having successwith it and want it for themselves. They are notusually concerned about safety or how much it willcost but would probably have many more questionsif the therapy was possible for them!

What types of information do you have toexplain?I usually explain and summarise the current state ofresearch into stem cell therapy and MS and explainthat the issues are more complex in neurologicaldiseases than other types of disease. I also oftenhave to point out that some of the centres wherestem cell therapy has been done are not scientific,often very expensive and have serious safetyconcerns. But it can be frustrating for patients whofeel they have no options, so we often also talk

about other current treatments that are workingand may be more suitable.

What are the main concerns your patientshave?The main concern is whether they can have accessto the therapy and whether it will help them recovertheir movement and ability, not just stop theprogression of MS. Many hope it will give them theirold bodies back. Some people also have concernsabout the source of the cells.

Which other sources of information havethey used?Mostly news stories on television and in papers, aswell as websites and speaking to other people withMS.

Do you suggest any sources to people whoask you about stem cell research?I always suggest people contact their national MSsociety because they will have user-friendlyinformation and be given neutral, unbiasedopinions about all therapy options. I alsospecifically refer them to MSIF’s website for moreinformation: www.msif.org.

Dr Pablo Villoslada.



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Awareness and the ethical question Only six percent (50 respondents) wereunaware of different types of stem cellsavailable and over 92 percent would considerhaving stem cell treatment, but many alsowanted to know about risks and how safe itwas, or what stage the research is currently at.Respondents were very specific about the kindof stem cells they found acceptable fortreatment – many were uncomfortable with theconcept of embryonic stem cells or against italtogether; however, it was seen by many as anethical dilemma, but some would still proceed“if there was no alternative”.

Information sources The Internet is a very popular source ofinformation about stem cell research, with anoverwhelming majority of 97 percent ofrespondents looking to the web for theirinformation; two-thirds (66 percent) also wentto MS Societies for more information.Interestingly, almost as many people looked tobooks and journals (35 percent) to researchstem cells and MS as those who went directlyto a neurologist (38 percent) for moreinformation.

The future for stem cell research In spite of 91 percent responding “yes” to thequestion: “Do you think that your national MS

Society should use funds for stem cell research?”,there were still many questions posed concerningstem cell treatment, ranging from what the riskswould be, to what types of MS the treatmentworks on, and how invasive the treatment wouldbe.

Conclusion Overall awareness is very high but knowledgeappears to be inconsistent in the field of stemcell research, with a high level of support fromrespondents about continuing with currentresearch and finding out more about stem celltreatment overall. Many use the word “cure” intheir comments; stem cell treatment is viewedpositively by many as a future treatment orsomething they would definitely consider if theirtype of MS worsened. The general outlook andreceptiveness for further research in this field isvery positive.

Stem cells onlinesurvey results Stem cell treatment is a very high-profile topic in current MS research. Over 92

percent of the respondents to the questionnaire had MS and the interest was well

reflected in the highest ever response – 886 – to any MS in focus online survey.


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The Stem Cell SiteThis site is part of the USgovernment’s official webportal, hosted by theNational Institutes ofHealth, and can be

reached at http://stemcells.nih.gov/info/basics.

The Stem Cell Site will engage and inform visitors,with its crisp format and easy to follow index andnavigation system. Topics include the uniqueproperties of all stem cells, embryonic stem cells,adult stem cells, similarities and differences betweenembryonic and adult stem cells and potential uses ofhuman stem cells. The site is comprehensive andhelpful, including directions to other sources ofinformation for the visitor. There is a glossary for mostof the difficult words, but following the text may bedifficult for those not already well-versed in biology.

The information is very extensive andcomprehensive, with all relevant aspects addressed.Diagrams (“cartoons”) are colourful and attractive,but require a good understanding of theterminology to interpret them comfortably (keepthat glossary handy!). Most motivated, patient anddiligent lay people will be able to follow the contentand understand the concepts, but many will find it achallenge. Healthcare professionals should have amuch easier time, since they already have thescientific foundation for this topic.

The Frequently Asked Questions link on the HomePage provides information in language moresuitable for the general audience. On the HomePage, the VII. Where can I get more information?link provides access to the University of Wisconsinsite, which is written in language more comfortablefor the uninitiated:www.news.wisc.edu/packages/stemcells/

Reviewed by Nancy Holland, Vice President,Clinical Programs, NMSS, USA.

A Health Handbook for Womenwith Disabilitiesby Jane Maxwell, Julia Watts Belserand Darlena DavidCopyright©2007 by HesperianFoundation, February 2007, ISBN:

978-0-942364-50-7 paperback.

This book is written for the millions of women withdisabilities around the world, including those withvision and hearing problems, difficulties walking,difficulties with speech, and those with learningimpairments.

The book aims to help women better care forthemselves and it will also assist family, friends,community health workers and caregivers whosupport women with disabilities.

There are 15 chapters, including mental health,taking care of your body, sexuality, family planning,caring for your baby, growing older with a disability,and support for caregivers.

The book offers very clear explanations related tothe different themes and potential situations. It iswritten in a very straightforward way and this,together with the many illustrations, makes it veryeasy to read and understand.

In my opinion the book is very thorough and itconsiders all of the important aspects andinformation for women dealing with theseconditions. I would highly recommend this book asan excellent introduction to anyone affected by orinterested in these matters.

I enjoyed this book very much and I am sure that youwill also find reading it both pleasurable and useful.www.hesperian.org

Reviewed by Maria Marta Castro, PwMSICmember for Argentina.

Reviews


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Astrocytes – also commonly called“neuroglia” or glia (Greek for glue), theseare star-shaped non-neuronal cells in thebrain: functions include the formation ofthe blood-brain barrier, providing nutrientsto the nervous tissue, and playing a role inthe repair and scarring process in thebrain.

Axons – nerve fibres, projections of nervecells, conducting electrical impulses awayfrom the neuron’s cell body (soma).

Biomarker – a substance used as anindicator of a biologic state; a biomarkercan be any kind of molecule indicating theexistence (past or present) of livingorganisms.

Cytokines – a group of proteins andpeptides used in organisms as signallingcompounds.

Endogenous – inside of the body.

Exogenous – outside of the body.

Experimental Autoimmune

Encephalomyelitis (EAE) – animalmodel of the human central nervoussystem (CNS) demyelinating diseases,including MS.

Graft-versus-host disease – a commoncomplication of bone marrowtransplantation between genetically non-identical (allogeneic) individuals. Thefunctional immune cells in the transplantedmarrow recognise the recipient as

“foreign”, mounting an immunologic attack.

Haematopoiesis – the formation ofblood cellular components; haematopoieticstem cells are the point of origin for all ofthe cellular components of cells.

Histology – anatomical study of themicroscopic structure of animal and planttissues; the microscopic study of tissues.

In vitro – within the glass; in a test tube;or performing an experiment in acontrolled environment, outside of a livingbody.

In vivo – within the living; in a livingorganism.

Ion channel expression – ion channelsare proteins that act as conductors,allowing water-loving ions to cross the oilylipid barrier of cell membranes into thewatery cytoplasm of a cell. Once there, theions enable basic physiological processessuch as growth, reproduction and musclecontraction.

Mesenchymal – multipotent stem cells.

Multipotent – the ability of a cell tobecome several different types of cell;multipotent haematopoietic cells canbecome any type of cell in the bloodsystem.

Oligodendrocytes – commonly called“neuroglia”, these are non-neuronal cells,whose main function is the myelination ofaxons in the central nervous system.

Glossary of terms used


Subscriptions The Multiple Sclerosis International Federationproduces MS in focus twice a year. With aninternational cross-cultural board, accessiblelanguage and free subscription, MS in focus isavailable to all those affected by MS worldwide. Goto www.msif.org/subscribe to sign up.

Previous issues are available in print or to download from our website:Issue 1 FatigueIssue 2 Bladder problemsIssue 3 FamilyIssue 4 Emotions and cognitionIssue 5 Healthy livingIssue 6 Intimacy and sexualityIssue 7 RehabilitationIssue 8 Genetics and hereditary aspects of MSIssue 9 Caregiving and MSIssue 10 Pain and MS

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wide. We have been active in the fight against MS

for over a decade. Through pharmacogenomics, we

are active in research towards understanding the

genetic basis of MS. Merck Serono has a long-term

commitment to people with MS through constant

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Documents

MSIF11 pp01-28 English - MS International Federation · The future for stem cell technology and MS This issue of MS in focus will discuss how advances in understanding stem cell biology