Schatteman G C, Hanlon H D, Jiao C, Dodds S G, Christy B A
Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa 52245, USA.
J Clin Invest. 2000 Aug;106(4):571-8. doi: 10.1172/JCI9087.
Endothelial cell progenitors, angioblasts, have been detected in the peripheral blood of adult humans, mice, and rabbits. These cells have been shown to incorporate into the endothelium of newly forming blood vessels in pathological and nonpathological conditions. Here we investigated the possibility that the CD34-expressing leukocytes (CD34(+) cells) that appear to be enriched for angioblasts could be used to accelerate the rate of blood-flow restoration in nondiabetic and diabetic mice undergoing neovascularization due 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 differentiated endothelial cells in culture than did their type 2 diabetic- or nondiabetic-derived counterparts. In vitro experiments suggest that hyperglycemia per se does not alter the ability of angioblasts to differentiate or of angioblast-derived endothelial cells to proliferate. In contrast, hyperinsulinemia may enhance angioblast differentiation but impair angioblast-derived endothelial cell survival or proliferation. Our findings suggest that CD34(+) cells may be a useful tool for therapeutic angiogenesis in diabetics.
内皮祖细胞,即成血管细胞,已在成年人类、小鼠和兔子的外周血中被检测到。这些细胞已被证明在病理和非病理条件下可整合到新形成血管的内皮中。在此,我们研究了一种可能性,即似乎富含成血管细胞的表达CD34的白细胞(CD34(+)细胞)能否用于加速因后肢缺血而进行血管新生的非糖尿病和糖尿病小鼠的血流恢复速度。CD34(+)细胞并未加速非糖尿病小鼠的血流恢复,但却显著提高了糖尿病小鼠的血流恢复速度。此外,与来自2型糖尿病或非糖尿病个体的CD34(+)细胞相比,1型糖尿病患者来源的CD34(+)细胞在培养中产生的分化内皮细胞更少。体外实验表明,高血糖本身并不会改变成血管细胞的分化能力或成血管细胞来源的内皮细胞的增殖能力。相反,高胰岛素血症可能会增强成血管细胞的分化,但会损害成血管细胞来源的内皮细胞的存活或增殖。我们的研究结果表明,CD34(+)细胞可能是糖尿病患者治疗性血管生成的一种有用工具。