CELL TRANSPLANTS ASIA LTD
Peter K. Law, Ph.D.
Acute MI
Limited cardiomyocyte proliferation
Stem cell infiltration/injection fibroblasts ? SCAR
Myoblast injection ? MUSCLE
Cell culture is the only way to generate new, live cells that upon transplantation will survive, develop, and function to revitalize a degenerative organ
M
50mm
MTT is a gene therapy
Transfection normal genome in nucleus
Vehicle myoblasts
Mechanism natural cell fusion
Myoblast Properties
=Divided extensively
=Migrates
=Fuses naturally to form syncytia
=Loses MHC-1 antigens after fusion
=Develops to occupy 50% of body
weight
4-WEEKS INFARCTED
MYOBLASTS
2 g BIOPSY
Open Heart
Implantation
20-y.o. HEALTHY DONOR
Cell Culture
6-week
cyclosporine
Methods to Demonstrate Proof of Concept
3 Mechanisms of Heart Cell Therapy/ Proof of Concept
Xenograft of Lac-Z labelled human myoblasts into 30 porcine hearts
Myofibers
Cardiomyocytes
Heterokaryotic fibers
more myogenic cells with regenerative activity
more contractile filaments
increase contractile force
A
B
C
Human Myoblasts. FISH probes specific for human chromosomes 22.
Control pig myocardium with no myoblast implant. FISH probes for human chromosomes 22 and for pig chromosomes 1 and 10.
Pig myocardium with myoblast implants showing heterokaryotic cardiomyocyte.
Figure 1a Figure 1b
Figure 1c
A
B
C
D
A
B
C
D
AUTOGRAFT
No immunosuppression
ALLOGRAFT
PROS
CONS
CONS
2-mo immunosuppression
Cell culture takes 1-mo
Graft delay scar
Elderly cells less regenerative
High QA/QC costs for each individual graft
Host limitation
Infected/mutated host tissues may contaminate system
PROS
Good cells readily available
Grafting within 12 hr scar
Young cells rejuvenate
Low QA/QC costs for 50 grafts at a time
Unlimited supply
Patients with infections and genetic diseases can be treated
Allografts Need Pure Myoblasts
Desmin immuno-positive, not CD-56
Fibroblast contamination ? SCAR
Fibroblast MHC-I antigens ? inflammatory graft rejection
MYOBLASTS
2 g BIOPSY
20-y.o. HEALTHY DONOR
Cell Culture
Open Heart
Implantation
After CABG
8-week
cyclosporine
CAD, Chronic MI
63-y.o.
49-y.o.
Methods to Demonstrate Feasibility/Safety
Before
3 Months After
6 Months After
63 y.o. male, CAD, Chronic MI
1.1 Billion pure cGMP myoblasts
100 x 106 cells/mL, 18 injections
2-mo cyclosporine
Perfusion defect reduced
14.6% increase in EF after 3-mo
40.0% increase in EF after 12-mo
CCS-Class IV ? CCS-Class I-II
Wall thickening >3mm
Local akinesis disappeared
Before
3 Months After
9 Months After
49 y.o. male, CAD, Chronic MI
1.2 Billion pure cGMP myoblasts
100 x 106 cells/mL, 19 injections
2-mo cyclosporine
Perfusion defect reduced
10.5% increase in EF after 3-mo
35.6% increase in EF after 12-mo
CCS- Class IV ? CCS- Class I-II
Wall thickening > 3mm
Local akinesis disappeared
Angiomyogenesis with VEGF or TGF-? Myoblasts transduced with non-viral vector
90% endovascular delivery
10% epicardial, with CABG
Heart Transplant
$250,000 procedure + $1 million ICU +
~$150,000 life-long immunosuppression
HCT Autograft $100,000
HCT Allograft $20,000
Caucasian
Asian
MTT: Potential Treatment for
=Neuromuscular =Bone Cartilage
diseases degeneration
=Cardiomyopathy =hGH deficiency
=Cancer =Hemophilias
=Diabetes =Islet allograft
=Anemia rejection
=Pain =Aging
MTT PLATFORM
Cell Transplantation
Genome Therapy
Tissue Engineering
For Collaboration
1-905-508-2021
86-13501010427
65-91377296
Email: peter@celltherapy.com
celltps@pacific.net.sg