1. EMERGING ROLE OF STEM CELLS In CARDIOVASCULAR THERAPY
Dr. K. K Haridas MD, DM (Card) DNB (card)
Chairman - Department of cardiology – A.I.M.S Cochin 26

2. Why Rejenuate the Heart Muscle ?
THE PROBLEM :
~ 30 million suffer from heart failure world wide
~ 3-4 million develop hear failure every year
CAUSES OF VENTRICULAR REMODELLING
Acute Myocardial Infarction
Cardiomyopathy
Valvular congenital heart disease
OUTCOMES
<1% of all hear failure patients receive donor hearts or assist devices
Annual mortality in hear faisure is 7.5 to 38%

3. Is the heart a terminally differentiated organ ?
The Question
Is the heart a terminally differentiated organ ?

4. !
The Answer !
No.

5. Historical Evidence – The basis
Men the who received sex mismatched donor hearts shows primitive cells bearing Y chromosomes which expressed the markers of cardiomyocytes, smooth muscle cells and endothelial cells (Quainani et al.)

6. Chameleon “ Fountan of Hope”
Stem cells
(Genetic)
(Micro environment)
Trans Differentiation
Trans Determination
(VCAM/ICAM/MMP)
(Cytokines VEGEF)
“Homing” ability

7. Foetal Cardiomyocytes
Ideal cell replacement
Ultrastructural integratian
Good functional improvement of LV
Limitations
Limited source / ethics
Immunogenicity
Ischemia sensitivity

8. Embryonal stem cells Differentiation Early stage : Pacemaker cells
Intermediate : Myocardial cell
Late : Nodal, His purkinjee cells
Note:
Day 5 Human blastocyst  inner cell mass
High yield of cardiomyocytes
? Useful in bio-engineering
Human spare parts factory

9. LIMITATIONS ETHICAL ISSUES IMMUNOGENICITY TERATOCARCINKOMA
ARRHYTHMOGENESIS

10. Autologous stem cells
Easy to source
Non immunogenic

11. Cell Therapy in Failing Heart
GOAL
Transfer of functional myocytes to heart – Improve its function
The DEALS “ Homing of grafted cells”
Engraft into non functional scar
Electromechanical coupling and synchronisation
Neo angiogenesis and myogenesis
Good craft survival
Low immunogenecity
Ethical acceptance
Low oncogenicity
Case of application

12. Stem cells for myocardial regeneration
HETEROLOGOUS
Fetal cardiomyocytes
Embryonal stem cells
AUTOLOGOUS
Skeletal myoblast
Endothelial progenitors
Bone marrow stem cells

13. Stem cells therapy Cardiovascular note Infarct repair
Cardiomyopathy treatment
End stage coronary artery disease

14. SKELETAL MYOBLASTS Satellite cells found in skeletal muscle
Mature into slow twitch fibers
No ultra structural integration
Stretch-ion channel & direct trans-membrane activation
Scaffolding effect – Cell to cell fusion

15. Limitations of skeletal myoblasts
Arrythmogenesis
Electrical heterogenically
Asynchronous ion channel activity
Post inflammatory
Recutry pathway

16. Bone marrow stem cells HEART Hemapoeitic Stem cells T-2%
Endothelial Progenitor cells <0.05% (Stromal stem cells)
(Lin – c Kit (+ve) ; AC 133+)
CD 34+
Transplantation
HEART
Translocation
(Endogenous stem cell mobilization)
G – CSF
GM - CSF
CARDIOMYOCYTES
Endothelium sm cells

17. Increased vascular permeability
Homing – in of Graft
Ischemia ; Hypoxia
Cytokines
Increased vascular permeability
V CAM
I CAM
VEGF – 2
GCSF
SDF – Increased
MMP 9

18. Some Unresolved Issues
Which Cells(s) type ?
Which mode of delivery
Tailored Administration in clinical scenarios
What dose ?
Adjunctive therapy

19. Some Unresolved Issues
Immunogenecity
How effective / How risky
Optimal timing of therapy
Ethical timing of therapy
Durability of therapy

20. You see things; and you say “Why” But I dream things that never were;
And I say “Why not”
G.B. Shaw

21. In youth we learn In age we understand
Mary Von Ebner Eschenbach