Cardiac cell repair therapy

Approached by replacement, rejuvenation or restoration, and regeneration.

Replacement refers to tissue transplantation.

Rejuvenation or restoration indicates the activation of cardiac stem cells or other stem cells.

Regeneration relies on the progenitor or stem cell engraftment to form myocytes.

It is postulated that nonviable myocardium can be regenerated or repaired by stem or progenitor cells.

Bone marrow derived cells, including mononuclear cells and mesenchymal stem cells can improve left ventricular remodeling in acute and chronic ischemic cardiomyopathy.

The heart myocyte is considered terminally differentiated and its response to injury is hypertrophy and not hyperplasia.

Fewer than 50% of cardiac myocytes are exchanged during life, indicating the heart has an inadequate ability to repair itself after ischemic injury.

In infarction induced heart failure the myocyte deficit is associated with approximately a 25% loss of the left ventricle involving 1 billion myocytes (Murry CE).

Successful heart muscle regeneration must be achieved on a large scale and be able to have synchronous contraction and electromechanical coupling with angiogensis.

Meta-analyses of bone marrow mononuclear cell delivery to the infarct zone after acute myocardial infarction has shown small improvements in left ventricular function after successful reperfusion (Clifford DM et al).

Following an acute MI the myocardium and bone marrow undergo changes that affect stem or progenitor cell engraftment and survival.

Delivering bone marrow mononuclear cells 5 to 7 days after acute myocardial infarction results in greater improvement in left ventricular ejection fraction compared with delivery of the same cells earlier ( Repair-AMI trial).

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