EMERGING ROLE OF STEM CELLS In CARDIOVASCULAR THERAPY

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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

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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
• lt1 of all hear failure patients receive donor
  hearts or assist devices
• Annual mortality in hear faisure is 7.5 to 38

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• ?
• The Question
• Is the heart a terminally differentiated organ ?

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• !
• The Answer !
• No.

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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.)

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• Chameleon Fountan of Hope

Stem cells
(Genetic)
(Micro environment)
Trans Differentiation
Trans Determination
(VCAM/ICAM/MMP)
(Cytokines VEGEF)
Homing ability
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Foetal Cardiomyocytes

• Ideal cell replacement
• Ultrastructural integratian
• Good functional improvement of LV
• Limitations
• Limited source / ethics
• Immunogenicity
• Ischemia sensitivity

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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

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• LIMITATIONS
• ETHICAL ISSUES
• IMMUNOGENICITY
• TERATOCARCINKOMA
• ARRHYTHMOGENESIS

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Autologous stem cells

• Easy to source
• Non immunogenic

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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

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• Stem cells for myocardial regeneration

• HETEROLOGOUS
• Fetal cardiomyocytes
• Embryonal stem cells

• AUTOLOGOUS
• Skeletal myoblast
• Endothelial progenitors
• Bone marrow stem cells

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Stem cells therapy

• Cardiovascular note
• Infarct repair
• Cardiomyopathy treatment
• End stage coronary artery disease

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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

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Limitations of skeletal myoblasts

• Arrythmogenesis
• Electrical heterogenically
• Asynchronous ion channel activity
• Post inflammatory
• Recutry pathway

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Bone marrow stem cells
Hemapoeitic Stem cells T-2
Endothelial Progenitor cells lt0.05 (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
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Homing in of Graft
Ischemia Hypoxia
V CAM I CAM
Cytokines
Increased vascular permeability
VEGF 2 GCSF SDF Increased MMP 9
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Some Unresolved Issues

• Which Cells(s) type ?
• Which mode of delivery
• Tailored Administration in clinical scenarios
• What dose ?
• Adjunctive therapy

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Some Unresolved Issues

• Immunogenecity
• How effective / How risky
• Optimal timing of therapy
• Ethical timing of therapy
• Durability of therapy

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• You see things and you say Why
• But I dream things that never were
• And I say Why not
• G.B. Shaw

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• In youth we learn
• In age we understand
• Mary Von Ebner Eschenbach