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Monitoring Stem Cell Research 
where transplanted cardiomyocyte precursors contained an 
admixture of cells also giving rise to vascular structures, survival and 
function of the newly formed cardiomyocytes has been significantly 
augmented. 
In one study, direct injection of whole rat bone marrow into a 
cryo-damaged heart resulted in neovascularization, cardiomyocyte 
regeneration and functional improvement More recently, 
systemic delivery of highly purified bone marrow-derived 
hematopoietic stem cells in lethally irradiated mice contributed to 
the formation of both endothelial cells and long-lived cardiomyocytes 
in ischemic hearts Most strikingly, significant improvement in 
cardiac function of mice who had previously undergone LAD ligation 
was demonstrated after direct myocardial injection of syngeneic 
bone marrow-derived stem cells, defined on the basis of c-kit (GDI 17) 
expression This population of cells contains a mixture of cellular 
elements in addition to cardiomyocyte precursors, including CD117- 
positive endothelial progenitors (see below). These cells were found 
to proliferate and differentiate into myocytes, smooth muscle cells 
and endothelial cells, resulting in the partial regeneration of the 
destroyed myocardium and prevention of ventricular scarring. 
Together, these findings raise the intriguing possibility that for long- 
term in vivo viability and functional integrity of stem cell-derived 
cardiomyocytes it may be necessary to induce neovascularization by 
co-administration of endothelial cell progenitors (see below). 
Endothelial Precursors And Formation Of Vascular Structures 
During Embryogenesis. In order to develop successful methods for 
inducing neovascularization of the adult heart, one needs to 
understand the process of definitive vascular network formation 
during embryogenesis. In the pre-natal period, hemangioblasts 
derived from the human ventral aorta give rise to cellular elements 
involved in both vasculogenesis, or formation of the primitive 
capillary network, and hematopoiesis In addition to 
hematopoietic lineage markers, embryonic hemangioblasts are 
characterized by expression of the vascular endothelial cell growth 
factor receptor-2, VEGFR-2, and have high proliferative potential 
with blast colony formation in response to VEGF Under the 
regulatory influence of various transcriptional and differentiation 
factors, embryonic hemangioblasts mature, migrate and differentiate 
to become endothelial lining cells and create the primitive 
vasculogenic network. The differentiation of embryonic 
hemangioblasts to pluripotent stem cells and to endothelial 
precursors appears to be related to co-expression of the GATA-2 
PRE -PUBLICATION VERSION 
