Zhou B, Bi Y Y, Han Z B, Ren H, Fang Z H, Yu X F, Poon M-C, Han Z C
State Key Laboratory of Experimental Hematology, National Research Center for Stem Cell Engineering and Technology, Institute of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.
J Thromb Haemost. 2006 May;4(5):993-1002. doi: 10.1111/j.1538-7836.2006.01906.x.
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.
This study aimed to confirm the compromised efficiency of diabetic M-PBMNCs in therapeutic neovascularization, and to determine the underlying mechanisms of this impairment.
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. Non-invasive 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.
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.
Diabetes reduced the capacity of M-PBMNCs to augment neovascularization in ischemia.
动员外周血单个核细胞（M-PBMNCs）自体移植是改善糖尿病患者严重肢体缺血（CLI）的一种新方法。然而，糖尿病患者的内皮祖细胞（EPCs）功能失调，在缺血诱导的新血管形成中受损。
本研究旨在证实糖尿病M-PBMNCs在治疗性新血管形成中的效率受损，并确定这种损害的潜在机制。
将来自17例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。评估这三组之间的肢体血液灌注、活动评分、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情况。使用非侵入性实时成像和组织病理学检测移植的M-PBMNCs在体内的作用。检测EPCs的增殖和黏附情况。使用体外血管网络整合和基质胶栓试验来测试M-PBMNCs的促新血管形成作用。
糖尿病M-PBMNCs移植也改善了新血管形成，但程度低于非糖尿病M-PBMNCs。这与糖尿病M-PBMNCs分化为EPCs的能力受损、体外整合到血管样小管中的能力受损、参与皮下基质胶栓中血管样结构形成的能力受损以及刺激周细胞/平滑肌细胞募集的能力受损有关。此外，血管生成存在损害，这与糖尿病M-PBMNCs来源的EPCs黏附能力降低有关。
糖尿病降低了M-PBMNCs在缺血中增强新血管形成的能力。
