Ischemic vascular damage can be repaired by healthy, but not diabetic, endothelial progenitor cells
Ischemic vascular damage can be repaired by healthy, but not diabetic, endothelial progenitor cells
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DOI：
10.2337/db06-1254
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发表时间：
2007-04-01
期刊：
影响因子：
7.7
通讯作者：
Grant, Maria B.
中科院分区：
文献类型：
--
作者：
Caballero, Sergio;Sengupta, Nilanjana;Grant, Maria B.
内皮前体细胞（EPC）在血管修复和维持中起关键作用，并且它们的功能受到糖尿病的影响。我们先前证明，从糖尿病患者中分离出的EPC具有深远的体外迁移。我们询问来自正常个体的EPC是否能够更好地重新填充慢性（糖尿病）和急性（缺血/再灌注[I/R]损伤和新生儿氧诱导的视网膜病毒[OIR]）的眼球血管造影的动物模型的慢性（糖尿病）和急性（缺血/R]损伤和急性（缺血/R）中的EPC。损害。链霉菌素诱导的糖尿病小鼠，自发的糖尿病BBZDR/WOR大鼠，具有I/R损伤的成年小鼠或带有OIR的新生小鼠在玻璃体中注射，或者在玻璃体中注射了荧光标记的CD34（+）细胞的全身循环。和性别匹配的健康对照对象。在管理细胞后的特定时间内，对细胞毛细血管的血管修复程度进行了免疫组织学和定量评估。在所有四个模型中，健康的人（HU）CD34（+）细胞连接并同化为脉管系统，而来自糖尿病供体的细胞均无法整合到受损的脉管系统中。这些研究表明，健康的HUCD34（+）细胞可以有效地修复受伤的视网膜，并且糖尿病患者的血管修复有缺陷。有缺陷的EPC可以适合于细胞自然鲁棒稳健函数的药理操作和恢复。
Endothelial precursor cells (EPCs) play a key role in vascular repair and maintenance, and their function is impeded in diabetes. We previously demonstrated that EPCs isolated from diabetic patients have a profound inability to migrate in vitro. We asked whether EPCs from normal individuals are better able to repopulate degenerate (acellular) retinal capillaries in chronic (diabetes) and acute (ischemia/reperfusion [I/R] injury and neonatal oxygen-induced retinopathy [OIR]) animal models of ocular vascular damage. Streptozotocin-induced diabetic mice, spontaneously diabetic BBZDR/Wor rats, adult mice with I/R injury, or neonatal mice with OIR were injected within the vitreous or the systemic circulation with fluorescently labeled CD34(+) cells from either diabetic patients or age- and sex-matched healthy control subjects. At specific times after administering the cells, the degree of vascular repair of the acellular capillaries was evaluated immunohistologically and quantitated. In all four models, healthy human (hu)CD34(+) cells attached and assimilated into vasculature, whereas cells from diabetic donors uniformly were unable to integrate into damaged vasculature. These studies demonstrate that healthy huCD34(+) cells can effectively repair injured retina and that there is defective repair of vasculature in patients with diabetes. Defective EPCs may be amenable to pharmacological manipulation and restoration of the cells' natural robust reparative function.