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EMERGING ROLE OF STEM CELLS In CARDIOVASCULAR THERAPY

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. Why Rejenuate the Heart Muscle ? . THE PROBLEM : ~ 30 million suffer from heart failure world wide

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EMERGING ROLE OF STEM CELLS In CARDIOVASCULAR THERAPY

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  1. EMERGING ROLE OF STEM CELLS InCARDIOVASCULAR 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. ? 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. Stem cells Chameleon “ Fountan of Hope” (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 Hemapoeitic Stem cells T-2% Endothelial Progenitor cells <0.05% (Stromal stem cells) (Lin – c Kit (+ve) ; AC 133+) CD 34+ HEART Translocation Transplantation (Endogenous stem cell mobilization) G – CSF GM - CSF CARDIOMYOCYTES Endothelium sm cells

  17. Homing – in of Graft Ischemia ; Hypoxia V CAM I CAM Cytokines Increased vascular permeability 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

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