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 in cardiovascular therapy

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

why rejenuate the heart muscle
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%
slide3
?

The Question

Is the heart a terminally differentiated organ ?

slide4
!

The Answer !

No.

historical evidence the basis
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.)

slide6

Stem cells

Chameleon “ Fountan of Hope”

(Genetic)

(Micro environment)

Trans Differentiation

Trans Determination

(VCAM/ICAM/MMP)

(Cytokines VEGEF)

“Homing” ability

foetal cardiomyocytes
Foetal Cardiomyocytes
  • Ideal cell replacement
  • Ultrastructural integratian
  • Good functional improvement of LV

Limitations

  • Limited source / ethics
  • Immunogenicity
  • Ischemia sensitivity
embryonal stem cells
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
slide9
LIMITATIONS
    • ETHICAL ISSUES
    • IMMUNOGENICITY
    • TERATOCARCINKOMA
    • ARRHYTHMOGENESIS
autologous stem cells
Autologous stem cells
  • Easy to source
  • Non immunogenic
cell therapy in failing heart
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
slide12
Stem cells for myocardial regeneration
  • HETEROLOGOUS
  • Fetal cardiomyocytes
  • Embryonal stem cells
  • AUTOLOGOUS
  • Skeletal myoblast
  • Endothelial progenitors
  • Bone marrow stem cells
stem cells therapy
Stem cells therapy
  • Cardiovascular note
  • Infarct repair
  • Cardiomyopathy treatment
  • End stage coronary artery disease
skeletal myoblasts
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
limitations of skeletal myoblasts
Limitations of skeletal myoblasts
  • Arrythmogenesis
    • Electrical heterogenically
    • Asynchronous ion channel activity
    • Post inflammatory
    • Recutry pathway
bone marrow stem cells
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

homing in of graft
Homing – in of Graft

Ischemia ; Hypoxia

V CAM

I CAM

Cytokines

Increased vascular permeability

VEGF – 2

GCSF

SDF – Increased

MMP 9

some unresolved issues
Some Unresolved Issues
  • Which Cells(s) type ?
  • Which mode of delivery
  • Tailored Administration in clinical scenarios
  • What dose ?
  • Adjunctive therapy
some unresolved issues19
Some Unresolved Issues
  • Immunogenecity
  • How effective / How risky
  • Optimal timing of therapy
  • Ethical timing of therapy
  • Durability of therapy
slide20
You see things; and you say “Why”

But I dream things that never were;

And I say “Why not”

G.B. Shaw

slide21
In youth we learn

In age we understand

Mary Von Ebner Eschenbach

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