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Prof. Dr.Klaus Heese!
General (Comparative) Biology
Biomedical Engineering !!
Prof. Dr.Klaus Heese!
Why General Biology, Molecular Cell Biology & Biochemistry ?
Introduction!
!! Translational Research Regenerative Medicine, Cell therapy, Robotics Surgery, Surgical Assistance System, Surgery Training System, New Diagnostic Imaging
!! CPC Operation !! Future Medical Technology
Basic Research on stem cells and biomaterials Introduction of IT to Surgical Suites
!! Physician-oriented Clinical Trial !! Education / Human Resource Development !! Patent Counseling, Intellectual Property Strategy
BME-CTR’s activity
BioMedical Engineering-Center for Translational Research (BME-CTR)"
Interdisciplinary Basic Research -!Life sciences (Bio, Chem, Phys) -!Engineering -! etc.
Clinical Application
Practical Application Commercialization
academia / industry
researchers Pharmaceutical
companies
Translational
Research Phase III
Phase I Phase II
Mega Study
Phase I/II
IND
Pilot clinical trial
hospitals Translation of the findings in basic research
more quickly and efficiently into medical practice
Phase II
Phase I/II
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New drug application
Basic research
First in Man
We are here!
Biomedical Engineering – Translational Research dmi of Osaka University
----> compare with KBIO (www.kbio.kr) Global Biomedical R&D Hub, Osong, Medical Innovation Foundation
----> compare with KBIO (www.kbio.kr) Global Biomedical R&D Hub, Osong, Medical Innovation Foundation
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Medical Center for Translational and Clinical
Research
Department of Medical Innovation Osaka University Hospital
Osaka University and Northern Osaka Bio Cluster
Osaka University Graduate School of Medicine is one of the nation’s most active medical school s and its hospital is also recognized as a top-
ranked hospital for its high-quality medical services.
Together with The National Cardiovascular Center and Saito Life Science Park, this area composes a cluster of academia, industry and practice in
medical science field.
EXPO ’70 Park and Tower
Saito Area - Nibio National Cerebral and Cardiovascular Center
Biomedical Tissue Engineering – dmi of Osaka University
Office Zone
Preclinical Research Zone
Collaboration Zone
Clinical Practice Zone
Cell Processing Center (CPC)
BioMedical Engineering-Center for Translational Research (BME-CTR)!
Office Zone
!!OOffices Conferencing room PC online monitoring system Genetic disease counseling room Data storage room
BioMedical Engineering-Center for Translational Research (BME-CTR)!
Preclinical Research Zone
!!Preclinical researches using human cells Latest equipments with validation
- Cell sorter - Real time PCR array system - Laser confocal microscope - SEM
BioMedical Engineering-Center for Translational Research (BME-CTR)!
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Collaboration Zone
!! labs for researchers from bio-companies !! Accessible to human stem cell bank
for research use
BioMedical Engineering-Center for Translational Research (BME-CTR)!
Therapy Zone
!! Operation room !!Intelligent image distribution system !! Connected to transplantation ward by skywalk !! Latest surgical equipments
- Endoscopic surgery robot “ZEUS” - Navigation system - Corn beam X-ray 3D imaging system
Transplantation Ward Skywalk
BioMedical Engineering-Center for Translational Research (BME-CTR)!
Medical center for Translational Research Osaka University Hospital
Cell Processing Center (CPC)
!!4 cell processing units under class 10000 !! Class100 in the biohazard cabinet !! All procedures are guided and recorded
by the procedure control system
R-CPX Programmable Cell Processing Robot
Medical center for Translational Research Osaka University Hospital Medical center for Translational Research Medical center for Translational Research Osaka University Hospital Osaka University Hospital
'
Heart
Eye
Bone
LVAS + Myoblast Sheet Transplantation
<32 37 Hydrophobic Hydrophilic !
Temperature-responsive Culture Surface
”
Myoblast sheet for Cardiomyopathy by Prof. Sawa
����
new bone
benign bone tumor with large
bone defect
bone marrow harvesting primary culture
(MSC expansion)
MSC integration to NEOBONE®
differentiation culture for 2 wks
cultured bone (final product)
transplantation of cultured bone
Bone Tissue Engineering Integrating Novel Ceramic Scaffold and Mesenchymal Stem Cells by Prof. Yoshikawa
Oral Mucosal Epithelium sheet for Corneal Reconstruction by Prof. Nishida
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Osaka University iPS Cell Clinical Research Network
Human iPS cell research center
IndustriesClinical
Departments Laboratories
Center for iPS Cell Research and Application(CiRA)Shinya Yamanaka Group
The project for realization of regenerative medicineKyoto University integrated hub for iPS cell reserch
needsneeds seeds
cell
collaboration
production,culture, technical instruction
cooperation
MTR
iPS cells
Cell bank
Industry-University Cooperation and Partnering Section
production,culture, technical instruction
collaboration
Regeneration therapy using myoblast sheet for the treatment of dilated type cardiomyopathy
Implantation
Cell isolation, culture Biopsy from skeletal muscle
Myoblast sheet CPC: cell processing center
GMP-compatible manufacturing
DCM patient Lamination
More improvement of heart function
Alternative to heart transplants
Freed from VAD at 3 months
Dec 15, 2007 Sankei Shinbun
Successful Clinical Result in 1st Case
Oral mucosal cell
Temperature-responsive culture dish
2 weeks culture
20
cultured epithelial sheet
Low temp
graft
Transplantation of cultured epithelial sheet to intractable corneal and conjunctival diseases
Fat tissue
37
3D-CAD based on CT data
Custom-design ceramics scaffold (Neobone)
Prefabrication of ceramic scaffold by CAM
Culture BM cells on ceramic scaffold and transplantation transplantation
Culture on ceramics
Transplantation of the cell / scaffold composite
Culture on ceramicsCulture on ceramics
Transplantation of the cell / Transplantation of the cell / Transplantation of the cell /
Roland DG, MDX-20
Pre Post
Cultured BM cells integrated with custom-design ceramic scaffold prefabricated by computer-aided modeling
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Preclinical study in MTR library and differentiation control of mesenchymal stem cell
Fat tissue Bone marrow Muscle Synovial membrane
Culture
Cell Bank Bio-reactor
Heart
Scale up of culture
Differentiation
3D Culture
Cell Bank Bio-reactor
R-CPX Programmable Cell Processing Robot
Medical Center for Translational Research, Osaka University Hospital
Norio HAYASHI, Professor, Department of Gastroenterology and Hepatology, Graduate Sch. of Medicine Tatsuya KANTO, Assoc. Professor, Department of Dendritic Cell Biology and Clinical Applications, Graduate Sch. Of Medicine
Collaboration Partner Researchers in Osaka Univ.
Research Abstract
Utilization Field & Concrete results
Immunotherapy against Gastrointestinal Cancers using Newly Developed Dendritic Cell Vaccine
!! Dendritic cell (DC) vaccine is a promising tool for the treatment of refractory cancers.
!! We successfully established “OPA-DC” capable of inducing more potent anti-tumor immune responses than conventional DC.
January 25, 2005: Approved by the review board of MCTR, Osaka University Hospital. At present, four patients received this new DC based immune therapy.
Osaka UniversityOsaka UniversityHow DC vaccine works
Ex vivoIn vivo
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CCL21TumorLN
cytotoxicity
CD4 T cellCD4 T cell
CD8 T cellCD8 T cell
Osaka UniversityOsaka UniversityOPA-DC
Conventional DCConventional DC
Newly Developed“OPA-DC”Newly Developed“OPA-DC”
Monocytes
Monocytes
day0 Day6�� Day7��DC
Maturation stimuliOK432 PGE1IFN-�
day0
DC
Maturation stimuliTNF-!, IL-6, PGE2, IL-1"
day2 day3
GM-CSFIL-4
GM-CSFIL-4
Short-term cultureShort-term culture
Osaka University
Therapy for intractable deafferentation pain with navigation-guided repetitive transcranial magnetic stimulation
Medical Center for Translational Research (MCTR), Osaka University Hospital
Youichi Saitoh, Associate Prof. Toshiki Yoshimine, Prof. Department of Neurosurgery Osaka University Graduate School of Medicine
Collaboration Partner Researcher in Osaka Univ.
Research Abstract
To establish more effective and less invasive therapy for intractable pain, navigation-guided repetitive transcranial magnetic stimulation (rTMS) is applied. In this trial, patient’s primary motor cortex is accurately stimulated with navigation-guided rTMS, and its effectiveness was evaluated.
Utilization Field & Concrete Results
Osaka University
The patient’s pain is evaluated by visual analogue scale before and after navigation-guided rTMS.
Wisker plot
Median 25%-75%
beforemiddle
after15min.
30min.60min.
90min.180min.
Time
3
4
5
6
7
8
9
10
11
VA
S
About 50% of the patients respond to rTMS. The pain relief continued for 3 hours after rTMS.
"! November 22, 2004: Approved by the review board of MCTR, Osaka University Hospital. "! At present (January 11, 2007), this treatment has finished in 27 cases.
Medical Center for Translational Research (MCTR), Osaka University Hospital
Takashi Fujikado, MD,PhD, Professor, Department of Applied Visual Science and Department of Ophthalmology
Collaboration Partner Researcher in Osaka Univ.
Neuroprotetcive Therapy for Ischemic Optic Neuropathy using Trans-corneal Electrical Stimulation
Methods of Electrical Stimulation
Trans-corneal electrical stimulation (TES) is a newly developed neuroprotective therapy for ischemic optic neuropathy, in which no effective therapy is established. The strategy of this treatment was based on the animal model in which TES improves the survival rate of retinal ganglion cells. The merit of this therapy is the safety and low invasiveness to patients which allows to treat in out-patient basis.
"! August 25, 2003: Approved by the review board of MCTR, Osaka University Hospital. "! At present (January 11, 2007), 15 patients received the therapy.
Research Abstract
Utilization Field & Concrete Results
Osaka University
Radio-frequency ablation of bone tumors under guidance by fluoro-navigation and intraoperative 3D-imaging
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Training Center for Endoscopic Surgery
Video monitor
Dry box with CCD camera
See-through box
VR training system (LapSim)
Textbook, results and cirtificate 620#$")1#'2#7"47'8'320)*-0)92)&8':;;<
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Paralyzed patients; Spinal cord injury
ALS, total locked-in Strokes, etc
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check also people at: http://bme.hanyang.ac.kr http://bmse.hanyang.ac.kr
2010.9.29 supine lateral
Interfascial Pterional Craniotomy
BMI : brain machine interface'%.#$'=42/#)*/*)>/*9)"+'?=@*AB
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[Ministry of Education, Culture, Sports,
Science and Technology, Japan]L=MN
Sensory System
Circulatory System
Motor System
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!"#$%"& '()*+%( Feedback system Shortening of development period
Cost reduction
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Artificil arm
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Cochlea Vision
I*7*.9+'J/K+#'I=&$/-'09)'L)KM.*#7'N*&*9+RetinaCircuit ModelSilicon Retina
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_7'Q"+21"'"31'N7'd"9.'?:;;[B'
Laplacian Gaussian (LG) -like Spatial Filtering
Y.2'-.c2b'C:7E'Z'C:7E++Y.2'-.c2b'C:7E'Z'C:7E++Y.2'-.c2b'C:7E'Z'C:7E++Y.2'-.c2b'C:7E'Z'C:7E++Y.2'-.c2b'C:7E'Z'C:7E++Y.2'-.c2b'C:7E'Z'C:7E++Y.2'-.c2b'C:7E'Z'C:7E++Y.2'-.c2b'C:7E'Z'C:7E++Y.2'-.c2b'C:7E'Z'C:7E++Y.2'-.c2b'C:7E'Z'C:7E++Contrast Enhancement
time
Gain
Temporal Filtering
Eye
Massively Parallel
FPGA (Field ProgrammableGate Array)
Log-polar Conversion
J7'KR03*8'L7'L"#-0*R"8'N7'e2$2)V").8'N7'd"9.8'?:;CCB Phosphene
Outer plexiform layer
Simulation
To µUBD
OP('B/:*./'09)'L)KM.*#7'N*&*9+
Silicon Retina System
External Processor
Wireless Interconnection
Analog InterfaceProgrammable Digital Unit
Stimulator
Signal ConverterInternal Processor
Sensor
Multi-Electrode Array
!UB Device
Visual Cortex
Input Image Visual Perception
Phosphene
Several 10!A5~10ms
100~200!s
time
Biphasic burst current stimulus
Wireless Interconnection
5.0ms~(=frame time)
5~ pulsestime1
23…
Electrode
Stimulus Timing
'
RoboticsWe have been focusing the emergent robotics that seeks for the design principle of robot behaviors through the interaction between the robot and its environment. We take the cognitive developmental robotics approach through which we try to understand the development of increasingly complex cognitive processes in natural and artificial systems and how such processes emerge through physical/ social interaction.
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Partnering - Promotion of collaboration Academic-industrial alliance
seeds from basic research ! clinical application and industrialization Collaboration research 12 companies The Community of Translational Research, Osaka University Hospital
Alliance, matching and information exchange for industrialization 55 companies
Medical-engineering alliance nano-biotechnology robotics surgery surgical guidance system surgical training system medical device design
International academic exchange McGowan Institute for Regenerative Medicine, Pittsburgh, PA, U.S.A. Hannover Clinical Trial Center, Hannover, Germany Cornell University, New York, NY, U.S.A. Cambridge University, UK Yonsei University, Korea The University of Pavia, Pavia, Italy
For more information, please contact below;
mirai@hp-mctr.med.osaka-u.ac.jp
Education
'
!"#$"%%&$"#
biomedical informatics
Crinical research professionals
Molecular imaging and drug design professionals
Predictive and social medicine professionals
Biomaterials biomedical engineering
General programs
biomedical informatics Biomaterials
Advanced programs
Crinical research Molecular imaging and drug
Professional programs
Ethics, Intellectual Property and Economics in Medical
Engineering
Outline of Clinical Medicine 2
Outline of Clinical Medicine 1
Bioinformatics
Clinical Pharmacology in Drug Development
Advanced Diagnostics and Treatment Engineering
Biomaterials Biosimulation
Drug Development
Fundamentals in Biomedical Statistics
Practical Clinical Trials
Design and Concept of Clinical Trials
Recent Advances in Biomedical Statistics
Clinical Drug Development Statistical Methods in Observational Studies
Biomedical Informatics
Clinical Research Professionals
Biomaterials
Advanced Diagnostics and Treatment Engineering
Clinical Medicine
Regulatory Science in Drug Development
Data Management of Clinical Trials
Introductory programs
Problem-based learningProblem-based learningProblem-based learning
Project-based learningSeminarSeminar
Workshop
Introductory programs Medical introduction
Medical engineering and informatics introductions
General programs Research-/Bio-ethics
Intellectural properties
Seminar on Clinical Research and Development of Drugs
'
Industries, Medical Institutions, Research Institutions
Development of Human Resources & Scientific Seeds
Master course
Doctor course Promotion of research in integrated field of medicine, engineering and informatics
and practical development of international human resources through
collaboration with private sectors
Re-Education
International partner/ associate institutes
UK: Oxford University New Zealand: University of Auckland
Italy: Ritzoli Orthopedics Research Institute France: Institute of Molecular and Cell Pharmacology (CNRS) etc.
Collaboration with regional educational &
research institutes In clinical medicine and
engineering, Comprehensive promotion of advanced research and
education Revitalization of the area
through creation of high-tech industries
Promotion of researches in
integrative fields of clinical medicine and
informatics Medical database
Advanced measurement and diagnostic system
Infrastructures in medical engineering and informatics
Collaboration with private sectors
Partnership with
gCOE program for Physiome and System
Biology ‘in silico Medicine’
!2).*17':;;ED:;;f
GRANT
[Japan Science and Technology Agency]
!2).*17':;;<D:;C;
GRANT[Ministry of Education,
Culture, Sports, Science and Technology,
Japan]
The future starts right now … http://www.technologyreview.com/featuredstory/425129/growing-heart-cells-just-for-you/ http://www.youtube.com/watch?v=IjU81a5TjZs http://www.guardian.co.uk/science/video/2012/may/23/beating-heart-muscle-cells-skin-cells-video
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