G-CSF-mobilized peripheral blood mononuclear cells from diabetic patients augment neovascularization in ischemic limbs but with impaired capability
G-CSF-mobilized peripheral blood mononuclear cells from diabetic patients augment neovascularization in ischemic limbs but with impaired capability
复制标题
DOI：
10.1111/j.1538-7836.2006.01906.x
复制
发表时间：
2006-05-01
影响因子：
10.4
通讯作者：
Han, ZC
中科院分区：
文献类型：
--
作者：
Zhou, B;Bi, YY;Han, ZC
工作背景：动员后外周血单个核细胞（M-PBMNCs）自体移植是改善糖尿病严重肢体缺血（CLI）的一种新方法。然而，来自糖尿病的内皮祖细胞（EPCs）在缺血诱导的新血管形成中功能障碍和受损。目的：本研究旨在证实糖尿病M-PBMNCs在治疗性新生血管形成中的受损效率，并确定这种损伤的潜在机制。研究方法：将来自17名糖尿病患者或健康对照的糖尿病M-PBMNCs或磷酸盐缓冲盐水（PBS）注射到链脲佐菌素诱导的糖尿病裸鼠的缺血肢体中。肢体血流灌注、动态评分。评价这三组之间的缺血损伤、毛细血管/纤维比率、小动脉密度、侧支血管形成和周细胞募集。采用无创性真实的时间成像和组织病理学检测移植的M-PBMNCs在体内的作用。检测EPCs的增殖和粘附能力。采用体外血管网掺入法和基质胶塞法检测M-PBMNCs的促血管新生作用。结果：糖尿病M-PBMNCs移植也改善了新生血管形成，但与非糖尿病M-PBMNCs移植相比，改善程度较低。这与糖尿病M-PBMNCs分化为EPCs的能力受损有关。在体外掺入血管样小管，参与皮下基质胶塞中血管样结构的形成，并刺激周细胞/平滑肌细胞的募集。此外，糖尿病M-PBMNCs血管生成受损，这与EPCs粘附能力降低有关。结论：糖尿病降低了M-PBMNCs在缺血中增加新生血管的能力。
Background: Autologous transplantation of mobilized peripheral blood mononuclear cells (M-PBMNCs) is a novel approach to improve critical limb ischemia (CLI) in diabetes. However, endothelial progenitor cells (EPCs) from diabetes are dysfunctional and impaired in ischemia-induced neovascularization. Objective: This study aimed to confirm the compromised efficiency of diabetic M-PBMNCs in therapeutic neovascularization, and to determine the underlying mechanisms of this impairment. Methods: Diabetic M-PBMNCs from 17 diabetic patients or healthy controls, or phosphate-buffered saline (PBS) were injected into the ischemic limbs of streptozotocin-induced diabetic nude mice. The limb blood perfusion, ambulatory score.. ischemia damage, capillary/fiber ratio, arteriole density, collateral vessel formation, and pericytes recruitment were evaluated between these three groups. Noninvasive real time image and histopathology were used to detect the in vivo role of transplanted M-PBMNCs. Proliferation and adhesion of EPCs were assayed. In vitro vascular network incorporation and matrigel plug assay were used to test the pro-neovascularization role of M-PBMNCs. Results: Transplantation of diabetic M-PBMNCs also improved neovascularization, but to a lesser extent from that observed with non-diabetic ones. This was associated with the impairment of diabetic M-PBMNCs capacity to differentiate into EPCs. to incorporate into vessel-like tubules in vitro, to participate in vascular-like structure formation in a subcutaneous matrigel plug, and to stimulate the recruitment of pericytes/smooth muscle cells. In addition, there was impairment in vasculogenesis, which was related to the reduced adhesion ability of EPCs from diabetic M-PBMNCs. Conclusions: Diabetes reduced the capacity of M-PBMNCs to augment neovascularization in ischemia.