Appendix M. 
377 
micro vascularity, cellularity, and numbers of capillaries, and by 
reduction in matrix deposition and fibrosis in comparison to controls. 
Neovascularization was significantly increased within both the 
mfarct zone and in the peri-infarct rim in rats receiving angioblasts 
compared with controls receiving saline or other cells which 
infiltrated the heart (e.g. CD34- cells or saphenous vein endothelial 
cells, SVEC). The neovascularization induced by human angioblasts 
was due to both an increase in capillaries of human origin as well as 
of rat origin, as defined by monoclonal antibodies v\hth specificity for 
human or rat CD31 endothelial markers. Capillaries of human origin, 
defined by co-expression of Dil fluorescence and human CD31, but 
not rat CD31, accounted for 20-25% of the total myocardial capillary 
vasculature, and was located exclusively 'within the central infarct 
zone of collagen deposition. In contrast, capillaries of rat origin, as 
determined by expression of rat, but not human, CD31, demonstrated 
a distinctively different pattern of localization, being absent within 
the central zone of collagen deposition and abundant both at the 
peri-infarct rim between the region of collagen deposition and 
myocytes, and between myoc'ytes. 
Human Angioblasts Protect Hypertrophied Endogenous 
Cardiomyocytes Against Apoptosis. By concomitantly staining rat 
tissues for the myocyte-specific marker desmin and performing DNA 
end-labeling using the TUNEL technique, temporal examinations 
demonstrated that the infarct zone neovascularization induced by 
injection of human angioblasts prevented an eccentrically-extending 
pro-apoptotic process e'vident in saline controls. Thus, at two weeks 
post-infarction, myocardial tissue of LAD-ligated rats who received 
saline demonstrated 6-fold higher numbers of apoptotic myocytes 
compared with that from rats receiving intravenous injections of 
human angioblasts. Moreover, these myocytes had distorted 
appearance and irregular shape. In contrast, myocytes from LAD- 
ligated rats who received human angioblasts had regular, oval 
shape, and were significantly larger than myocytes from control rats. 
Human Angioblasts Induce Sustained Regeneration/ Proliferation 
Of Endogenous Cardiomyocytes. In addition to protection of 
hypertrophied myoc'ytes against apoptosis, human angioblast- 
dependent neovascularization resulted in a striking induction of 
regeneration/proliferation of endogenous rat cardiomyocytes at the 
peri-infarct rim At two weeks after LAD ligation, rats receiving 
human angioblasts demonstrated numerous "fingers" of 
cardiomyocytes of rat origin, as determined by expression of rat MHC 
class I molecules, extending from the peri-infarct region into the 
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