干细胞移植治疗糖尿病下肢血管病变:细胞因子与血管新生

Stem cell transplantation in the treatment of diabetic lower extremity vascular disease: cytokines and angiogenesis

背景:干细胞在一定诱导条件下可分化成为血管性内皮细胞,可促进局部血管再生,生成新的毛细血管网,建立丰富的侧支循环,以达到改善和治疗下肢缺血的目的。目的:概述糖尿病下肢血管病变的发病机制,以及自体外周血干细胞移植、脐血干细胞移植、干细胞联合细胞因子移植治疗糖尿病下肢血管病变的基础研究和临床研究现状。方法:检索1983至2014年PubMed数据库、维普中文科技数据库及万方数据相关文献。英文检索词为"stem cells;stem cell transplantation;cord blood stem cell transplantation;diabetic angiopathies";中文检索词为"干细胞;干细胞移植;脐血干细胞移植;糖尿病血管病变"。结果与结论:糖尿病下肢血管病变的发病机制可能与免疫异常诱发炎症反应有关,目前还缺乏有效的治疗方法。干细胞移植治疗糖尿病并发症在动物模型及临床上均取得了一定的成果,其中应用较多的有胚胎干细胞、间充质干细胞和内皮祖细胞,其治疗糖尿病下肢血管病变的机制主要与其参与新生血管形成、启动和分泌相关因子、免疫调节以及干细胞的增殖和分化能力等有关。目前的基础研究主要限于单纯的干细胞移植和联合基因治疗的干细胞移植。与外周血干细胞移植相比,自体骨髓干细胞移植所采细胞更原始,操作更简单,费用更低。证实干细胞分泌的细胞因子不足以促进血管新生,而是刺激骨骼肌细胞分泌足够的细胞因子促进血管新生。目前干细胞的临床应用有很多的问题有待解决。

BACKGROUND： Stem cells under the certain condition can be induced to differentiate into vascular endothelial cells, to promote local angiogenesis and generate new capillary network and establish abundant collateral circulation, in order to achieve the purpose of improvement and treatment of lower limb ischemia. OBJECTIVE： To review the pathogenesis of diabetic lower extremity vascular lesions, and the basic and clinical development of autologous peripheral blood stem cell transplantation, umbilical cord blood stem cell transplantation, and stem cell transplantation combined with cytokines for the treatment of diabetic lower extremity vascular lesions. METHODS： A computer-based online search was performed in the PubMed database for relevant literatures published from 1983 to 2014. The keywords were ＂stem cells; stem cell transplantation; cord blood stem cell transplantation; diabetic angiopathies＂. RESULTS AND CONCLUSION： The pathogenesis of diabetic lower extremity vascular lesions may be associated with dysimmunity-induced inflammation. It is lack of effective treatment methods. Stem cell transplantation in animal models and clinical treatment of diabetes complications has obtained certain achievements. Embryonic stem cells, mesenchymal stem cells and endothelial progenitor cells are widely used,and the their mechanism underlying treatment of diabetic lower extremity vascular lesions is mainly related to their participation in new vessel formation, starting and secreting factors, immune regulation, and stem cell proliferation and differentiation ability. Currently, the basic research is mainly limited to simple stem cell transplantation and stem cell transplantation combined with gene therapy. Compared with peripheral blood stem cell transplantation, autologous bone marrow stem cell transplantation is preferred because of more primitive cells, simpler operation, and lower cost. Studies have confirmed that cytokines secreted from stem cells are not enough to promote angiogenesis, but stimulate the skeletal muscle cells to secrete enough factors for promoting angiogenesis. The current clinical application of stem cells has a lot of problems to be solved.