Partnership
Which partnership we can do?
We can collaborate each other in thefield of new medical technologies.
We can promote human resource
development including medicalstudents.

Heart failure patients received regenerative
therapy in Osaka University HospitalThank you for your attention !

Newly constructed Medical Innovation Center inOsaka University Graduate School of Medicine

Medical center for Translational Research

Osaka University Hospital
In 2002, MTR was established in Osaka
University Hospital as a translational
research center for the future medicaltechnology.

MTR’s activity
Translational Research development

CPF Operation
Future Medical Technology
Physician-sponsored Clinical Trial
Education / Human Resource Development
Patent Counseling, Intellectual Property Strategy

More than 45 TR projects supported in MTRMyocardial regeneration therapy by autologous stem cell transplantation
CPC
Bone tissue engineering – Integrating novel ceramic scaffold and mesenchymal stem cells
CPC
Transplantation of cultured epithelial sheet to intractable corneal and conjunctival diseases
CPC
Immunotherapy against gastrointestinal cancers using newly developed dendritic cell vaccine
CPC
 Therapy for intractable differentiation pain with navigation-guided repetitive transcranial magnetic stimulation
 Neuroprotective therapy for ischemic optic neuropathy using trans-corneal electrical stimulation
 Regeneration therapy using myoblast sheet with ventricular assist device against dilated type cardiomyopathy
CPC
Dendritic cells based immuno-chemotherapy against esophageal cancer
CPCOlfactory mucosa autografts in human spinal cord injury
Regeneration therapy using myoblast sheet against dilated type cardiomyopathy
CPC
Immune-induction therapy with HVJ-envelope gene therapy vector for advanced malignant melanoma
Development of Cancer Immunotherapy using peptide vaccine targeting WT1 protein
Islet cell transplantation
CPC
IL-6 inhibitor for amyloidosis associated with chronic inflammatory diseases
Drug development based on molecular mechanisms of onset of integration dysfunction syndrome
Cross-linked collagen scaffold: applications as a cartilage substitute and in drug development for diseases oflocomotive system
Tissue-engineered 3-D constructs of synovial stem cells for the treatment of intra-articular lesions
CPC
γ-PGA hydrophobic nano-particles as an adjuvant in liver cancer immunotherapyRegenerative medicine using adipose tissue-derived mesenchymal stem cells against periodontal diseases
CPC
Curative treatment of bullous epidermolysis using mesenchymal stem cells
CPC
Clinical trails on HB-EGF antagonist as a molecular-targeted drug for ovarian cancer
Feeder-free culture system for pluripotent stem cells using laminin fragment
Novel malaria vaccine activating innate immunity by CpG-ODNs for travelers to epidemic regions

Facilities in Osaka University Hospital for TR Promotion
Cell Processing Facility
Grade B CP units（CPF）

 6 cell processing units Grade B 3 isolator-type cell processing cabinets

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CP isolator

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管理室
BD Influx TM
Environmental monitoring

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Cell sorting under clean environment

in-room camera

Process control system

Incubator capable ofhypoxic condition

Facilities in Osaka University Hospital for TR Promotion

Clinical Trial Unit (CTU)- A Phase I trial facility

10 beds for Phase I clinical trialSample
Processing Room

Nurses’ Station
QQ

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冷ソファ2222

1.9×3.38m 1.9×3.38m 1.9×3.38m 1.9×3.38m
冷たな

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汚2

1.9×3.38m 1.9×3.38m 1.9×3.38m洗洗カ ウン ター

洗洗WCSW

Examination
Room

収納：リネン・車い222

1.9×3.38m 1.9×3.38m

2Accommodations forHealthy Subjects

尿冷蔵WCSWTV 60V

洗面所

洗濯Recreation Room/ Meeting RoomThe human resources developmentfor Regenerative medicine
Heart
Temperature-responsive Culture Surface
N-isopropylacrylamide”

37℃
Hydrophobic<32℃
Hydrophilic

LVAS + Myoblast Sheet Transplantation

BoneMyoblast sheet for Cardiomyopathy by Prof. Sawa

ＭＳＣEye①benign bone
②bone marrow
tumor with large③primary culture
harvestingbone defect(MSC expansion)④MSC integrationto NEOBONE®
differentiation
culture for 2 wks
new bone⑥transplantationof cultured bone

⑤cultured bone(final product)

Bone Tissue Engineering Integrating Novel Ceramic Scaffold
and Mesenchymal Stem Cells by Prof. Yoshikawa
Oral Mucosal Epithelium sheet for Corneal
Reconstruction by Prof. Nishida

Thank you for your attention !

Auto- or Allo-transplantation of iPSC-CMs
for clinical application
Allo-transplantation

Auto-transplantation

Patient

under immunosuppression

Patient

iPSC-CMs
Somatic cells“Ready-made”

iPSC-CMs Differentiation
Cardiomyogenic
differentiation

iPSCsiPS cell stock(CiRA, Kyoto)“Ready-made”

iPSCs
Healthy donor

Confirmation of Safety in each case

 Requiring “Long time and High costs”
Problems:
 Anxiety of safety
 High costs

Somatic cells

Problems:
 Immunological rejection Background
Donor
Homozygous-MHC

Heterozygous-MHC

More MHC-matched pairs

Craig J Taylor et al. Lancet 2005

MHC-matched
MHC-matched
MHC-matched
MHC-matched

50 MHC-homo iPS Cell lines would be
able to find a three locus match in 90%of the Japanese population

MHC-matched
MHC-matched

Recipient

Nakatsuji et al. Nature Biotech 2008

Evaluation of allogenic iPS cells using Primates(Crab-eating Macaque)Episomal transfection ofOct3/4, Sox2, Klf4, c-Myc and GFPPBMNC

HT1-homo iPSCsHomozygous HT1by Okita and Yamanaka of CiRA

①MHC-matched②MHC-mismatched+ TAC, MMF, PSL

HT1-homo iPSC-CM sheets+ TAC, MMF, PSL

CD3Heterozygous HT1Tacrolims (TAC) 2 mg/kg・day
Mycophenolate mofetil (MMF) 40 mg/kg・day
Prednisolone (PSL) 100 mg/kg・day

CD3

HT1 negative

Strategy for clinical application of iPSCBest iPS from CiRA Whole genome assay
 Functional assay of genemutation
 Methylation assay

Osaka Univ.
1.Differentiation andhigh volume culture
2. Elimination ofundifferentiated iPS
4. Regulation of allogenic
reaction

3. Evaluation oftumorigenesity Differentiated Cardiac cells
iPS cell sheets

NOG mouse
Acceleration ofdifferentiation

 Intermediate differentiation
Sarcoma?
 Undifferentiated iPS
Teratoma?