Emerging role of stem cells in cardiovascular therapy
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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 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

    • <1% 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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Stem cells

Chameleon “ Fountan of Hope”

(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 <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


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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


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