Blood-derived angioblasts accelerate blood-flow restoration in diabetic mice

Endothelial cell progenitors, angioblasts, have been detected in the periph eral blood of adult humans, mice, and rabbits. These cells have been shown to incorporate into the endothelium of newly forming blood vessels in patho logical and nonpathological conditions. Here we investigated the possibilit y that the CD34-expressing leukocytes (CD34(+) cells) that appear to be enr iched for angioblasts could be used to accelerate the rate of blood-flow re storation in nondiabetic and diabetic mice undergoing neovascularization du e to hindlimb ischemia. CD34(+) cells did not accelerate the restoration of flow in nondiabetic mice, but dramatically increased it in diabetic mice. Furthermore, CD34(+) cells derived from type 1 diabetics produced fewer dif ferentiated endothelial cells in culture than did their type 2 diabetic- or nondiabetic-derived counterparts. In vitro experiments suggest that hyperg lycemia per se does not alter the ability of angioblasts to differentiate o r of angioblast-derived endothelial cells to proliferate. In contrast, hype rinsulinemia may enhance angioblast differentiation but impair angioblast-d erived endothelial cell survival or proliferation. Our findings suggest tha t CD34(+) cells may be a useful tool for therapeutic angiogenesis in diabet ics.