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Monitoring Stem Cell Research 
infarct zone. The islands of cardiomyocytes at the peri-infarct rim in 
animals receiving human angioblasts contained a high frequency of 
rat myocytes with DNA activity, as determined by dual staining with 
mAbs reactive against cardiomyocyte-specific troponin I and rat 
Ki67. In contrast, in animals receiving saline there was a high 
frequency of cells with fibroblast morphology and reactivity with rat 
Ki67, but not troponin I, within the infarct zone. The number of 
cardiomyocytes progressing through cell cycle at the peri-infarct 
region of rats receiving human angioblasts was 40-fold higher than 
that at sites distal to the infarct, 20-fold higher than that found in 
non-inf arcted hearts, and 5-fold higher than that at the peri-infarct 
rim of animals receiving saline 
Neovascularization Of Acutely Ischemic Myocardium By Human 
Angioblasts Prevents Ventricular Remodelling And Causes 
Sustained Improvement In Cardiac Function. By 15 weeks post- 
infarction, rats receiving human angioblasts demonstrated markedly 
smaller scar sizes together with increased mass of viable 
myocardium within the anterior free wall. Whereas collagen 
deposition and scar formation extended almost through the entire 
left ventricular wall thickness in controls, with aneurysmal dilatation 
and typical EKG abnormalities, the infarct scar extended only to 20- 
50% of the left ventricular wall thickness in rats receiving CD34+ 
cells. Moreover, pathological collagen deposition in the non-infarct 
zone was markedly reduced in rats receiving CD34+ cells. At 15 
weeks, the mean proportion of scar/normal left ventricular 
myocardium was 13% in rats receiving CD34+ cells compared with 
36-45% for each of the other groups studied (saline, CD34-, SVEC). 
Remarkably, by two weeks after injection of human 
angioblasts, and in a parallel time-frame with the observed neo- 
vascularization, left ventricular ejection fraction (LVEF) recovered by 
a mean of 22%. This effect was long-lived, with LVEF recovering by a 
mean of 34% at the end of follow-up, 15 weeks post injection. Neither 
CD34- cells nor SVEC demonstrated similar effects. At 15 weeks 
post-infarction, mean cardiac index in rats injected with human 
angioblasts was only reduced by 26% relative to normal rats, 
whereas for each of the other groups it was reduced by 48-59%. 
Together, these results indicate that the neovascularization, 
reduction in peri-infarct myocyte apoptosis and increase in 
cardiomyocyte regeneration/proliferation observed at two weeks 
prevented myocardial replacement with fibrous tissue and caused 
sustained improvement in myocardial function. 
PRE-PUBLICATION VERSION 
