Myocardial Neovascularization by Adult Bone Marrow-Derived Angioblasts: Strategies for Improvement of Cardiomyocyte Function

In the pre-natal period hemangioblasts, derived from the human ventral aorta give rise to cellular elements involved in both hematopoiesis and vasculogenesis, resulting in formation of the primitive capillary network. Endothelial precursors with phenotypic and functional characteristics of embryonic hemangioblasts are also present in human adult bone marrow, and can be used to induce infarct bed vasculogenesis and angiogenesis after experimental myocardial infarction. The neovascularization results in decreased apoptosis of hypertrophied myocytes in the peri-infarct region, long-term salvage and survival of viable myocardium, reduction in collagen deposition, and sustained improvement in cardiac function. Autologous angioblasts may also be useful in cellular therapy strategies aiming to regenerate myocardial tissue after established heart failure. It is likely that protocols using cardiomyocyte/mesenchymal stem cells will require balanced co-administration of angioblasts to provide vascular structures for supply of oxygen and nutrients to both the chronically ischemic, endogenous myocardium and to the newly-implanted cardiomyocytes. Future studies will need to address the timing, relative concentrations, source and route of delivery of each of these cellular populations in animal models of acute and chronic myocardial ischemia.