CHALLENGES OF MYOGENESIS AND REPAIR OF THE HEART

A damaged myocardium cannot effectively regenerate and repair itself subsequent to either acute or chronic pathologic insult. The emerging field of cell transplantation has attempted to address some of the issues and has progressed from preclinical studies to proof-of-concept clinical studies conducted in humans. Different cell types are being researched, including autologous skeletal muscle-derived myoblasts, bone marrow-derived mesenchymal stem cells and autologous bone marrow-derived stem cells. Other ongoing efforts are seeking to promote homing of bone marrow-g g derived cells to convert to cardiomyocytes in the myocardium, enhancement of the ability of cardiomyocytes to replicate and efforts to derive pluripotent stem cells from human blastocysts. While a variety of other cell types such as embryonic cardiomyocytes and embryonic stem cells have been investigated through preclinical studies, they have not progressed to clinical applications, for logistic and ethical reasons. The goal of any such therapy is to restore both an angiogenic and a muscular component to the myocardium by replacing damaged, fibrous scar tissue with compliant, elastic muscle tissue that would convert an akinetic or dyskinetic scar into tissue that augments systolic and diastolic function. The unique ability of skeletal muscle-derived stem cells (myoblasts) to form myotubes within the infarcted zones of the heart has led to the promotion of early pilot studies in humans.1-5 A secondary benefit would be that the compliance of the scar would be modified such that the pathologic remodeling process would be altered and would progress towards the baseline normal state.6-8 The challenge of replacing a large amount of dysfunctional and necrotic tissue is immense, and the ability to deliver, retain and engraft cells into a mechanically disadvantaged and neurohormonally altered environment has yet to be adequately addressed.