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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

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Heart

Eye

Bone

LVAS + Myoblast Sheet Transplantation

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Temperature-responsive Culture Surface

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Myoblast sheet for Cardiomyopathy by Prof. Sawa

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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

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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

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Sensory System

Circulatory System

Motor System

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Cost reduction

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Artificil arm

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Pacemaker Brain Machine Interface

Cochlea Vision

I*7*.9+'J/K+#'I=&$/-'09)'L)KM.*#7'N*&*9+RetinaCircuit ModelSilicon Retina

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Laplacian Gaussian (LG) -like Spatial Filtering

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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

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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

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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

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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

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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’

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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