干细胞移植治疗下肢缺血性疾病的研究进展

Research development of stem cell transplantation in the therapy of limb ischemia

目的:治疗性血管生成是利用成血管诱导因子或内皮祖细胞,模拟体内血管生成的机制,从而达到促血管新生、改善侧支循环的目的。近年来基于内皮祖细胞的干细胞移植成为治疗性血管生成的研究热点,对干细胞和内皮祖细胞的生物特性、细胞移植在下肢缺血性疾病中的基础及临床研究进展作一综述。资料来源:应用计算机检索PUBMED 1997-01/2006-03期间的相关文章,检索词为“stem cell,endothelial progenitor cell,neovascularzation,ischemic limb”,并限定文章语言种类为English。同时计算机检索万方数据库1997-01/2006-03期间的相关文章,检索词为“干细胞,内皮祖细胞,血管新生,下肢缺血性疾病”,并限定文章语言种类为中文。资料选择:对资料进行初审,并查看每篇文献后的引文。纳入标准:文章所述内容应与干细胞或内皮祖细胞的生物特性、下肢缺血性疾病细胞移植的研究相关。排除标准:重复研究或Meta分析类文章。资料提炼:共收集到102篇相关文献,33篇文献符合纳入标准,排除的69篇文献为内容陈旧或重复。符合纳入标准的33篇文献中,3篇涉及干细胞和血管内皮祖细胞的生物学特性,16篇涉及干细胞移植治疗下肢缺血性疾病的基础研究,12篇涉及干细胞移植治疗下肢缺血性疾病的临床应用,2篇涉及存在的问题与展望。资料综合:干细胞是一类高度自我更新和分化潜能很强的细胞,具有多重分化活性,在特定微环境中可诱导分化为内皮细胞,具有血管活性。基础研究表明骨髓、外周血或脐血干细胞移植能使肢体侧支循环增加,有效改善后肢缺血。近些年来受到广泛关注的骨髓间充质干细胞扩增细胞能保持干细胞的部分特性,体外分化成血管壁结构成分,体内可促进缺血下肢血管新生。用来移植的干细胞数量有限,干细胞联合细胞因子移植具有更强大的促血管新生的作用。干细胞参与血管形成的机制主要有直接分化、成熟为新血管以及分泌血管内皮细胞生长因子等促进局部缺血组织的血管新生。临床研究表明自体骨髓干细胞或自体外周血干细胞移植治疗下肢缺血性疾病都取得了较好的临床效果,但仍然存在移植安全性、远期治疗效果、提高临床疗效等问题。结论:干细胞移植能促进下肢血管新生,已成为治疗下肢缺血性疾病的新方法。虽然有许多问题尚需解决,但该手段较传统的治疗方法有着无可比拟的优越性,发展空间广阔。

OBJECTIVE： Therapeutic vasculogenesis is the treatment by using angiogetic factors or endothelial progenitor calls to induce angiogenesis in vivo, improve neovascutarization and ameliorate collateral circulation. Recently transplantation of stem call basing on the endothelial progenitor call has become a hot topic of the therapeutic vasculogenesis. This article is to summarize the biologic character of stem call and endothelial progenitor call, preclinical research and clinical research of cell transplantation in the treatment of limb ischemia. DATA SOURCES： A computer-based online search was conducted in Pubmed database for English literatures about therapy of limb ischemia by stem calls published from January 1997 to March 2006 by using the key words of ＂stem call, endothelial progenitor cell, neovascularzation, ischemic limb＂. Meanwhile, Wanfang database was retrieved for the related articles in Chinese during the same period by imputing the same keywords. STUDY SELECTION： All the literatures ware screened firstly, and the citations of each article ware looked up. Inclusion criteria： articles about the biologic character of stem cell and endothelial progenitor call; study about treatment of limb ischemia by call transplantation. Exclusion criteria： similar study or article using Meta analysis. DATA EXTRACTION： A total of 102 articles ware collected, and 69 old or similar studies ware excluded whereas 33 articles met our criteria. Thereinto 3 articles ware about the biologic character of stem cell and endothelial progenitor call, 16 articles about preclinical research in the treatment of limb ischemia with stem call transplantation, 12 articles about clinical research in the treatment of limb ischemia with stem call transplantation, and 2 articles about existent problem and expectation. DATA SYNTHESIS： Stem call has the characteristic of self-rebirth and strong potential of differentiation. It can differentiate into many types of calls and can be induced to differentiate into endothelial call in special condition.. Preclinical researches indicate that transplantation of stem call from bone marrow, peripheral blood or cord blood can increase collateral circulation and improve the limb ischemia. Expanded bone marrow stromal calls can remain some specialty o.f stem call that is the focus of recent researches. It can in vitro differentiate into structure of blood vessel, in vivo improve vasculogenesis in ischemic limb. Although the quantity of stem call is limited, transplantation of stem call with call factor has better effect on vasculogenesis. The mechanism of vasculogenesis includes stem call form new blood vessel and excrete endothelial call growth factor, which induce vasculogenesis. Clinical researches indicate that autologous transplantation of bone marrow or peripheral blood stem call has acquired good effect on limb ischemia, but still exist many problems, such as the security of stem call transplantation, therapeutic efficacy for a long term, and how to improve the clinical effect, etc. CONCLUSION： Transplantation of stem call can induce vasculogenesis, which has become the new therapy of limb ischemia. Although many problems remain to be resolved, the therapy has unexampled advantage and wide development compared with the traditional ones.