基因修饰干细胞治疗心肌梗死：临床前和临床应用中的相关问题

背景：干细胞具有分化为心肌及血管的潜力,可使缺血部位心肌得以组织修复及血运重建。该特性使干细胞移植成为具有发展前景的治疗缺血性心脏病的新型疗法。但干细胞移植后的长期存活以及远期疗效问题仍是难题。基因修饰联合干细胞移植的出现为干细胞研究提供了新思路。目的：就现阶段用于心脏再生治疗的干细胞种类、治疗性基因的选择、移植载体与移植途径的探索及基因修饰干细胞在心血管治疗领域的临床应用进行概述。方法：应用计算机检索PubMed数据库中2006年1月至2013年12月关于干细胞的文章,在标题和摘要中以＂stem cells;genetic therapy;myocardial infarction;regenerative medicine;tissue construction＂为检索词进行检索。选择文章内容与干细胞有关者,同一领域文献则选择近期发表或发表在权威杂志文章。最终选择40篇文献进行综述。结果与结论：干细胞联合基因修饰疗法可显著增强移植后的疗效,骨髓间充质干细胞是目前应用最广泛的种子细胞之一,通过腺病毒及腺相关病毒介导的抗凋亡、促血管生成、抗炎症等基因修饰后的干细胞疗效将显著提高。基因修饰干细胞移植有潜力应用于包括心肌梗死在内的多种临床疾病,但其长期安全性仍有待进一步研究。

The preclinical and clinical application of genetically modified stem cells for the treatment of myocardial infarction

BACKGROUND： Stem cells possess the potential of differentiation into myocardium and vessels, which can be transplanted into myocardial ischemia parts for tissue repair and revascularization. Therefore, stem cell transplantation has emerged as a promising alternative therapeutic approach for the treatment of ischemic heart disease. However, the long-term survival and curative efficacy issue of stem cells remains a problem. The emergence of genetic modification in combination with stem cell transplantation for stem cell research provides a new way of thinking. OBJECTIVE： To explore stem cell types for cardiac regeneration therapy, the selection of the therapeutic gene, the genes vectors and transplantation way and to overview the clinical application of gene-modified stem cells in the field of cardiovascular disease. METHODS： A computer-based search of PubMed（2006-01/2013-12） was performed to collect articles about stem cells. The key words included ＂stem cells; genetic therapy; myocardial infarction; regenerative medicine; tissue construction＂. Articles related to stem cells published recently or in high-impact journals were initially surveyed and finally 40 articles were included and summarized. RESULTS AND CONCLUSION： The efficacy of stem cell transplantation may be significantly augmented bygenetic modification. Bone marrow mesenchymal stem cells are one of the most widely used seed cells currently. The anti-apoptosis, pro-angiogenic, anti-inflammatory genes mediated by the adeno-associated virus and adenovirus were transfected into stem cells, so that the curative effect of stem cell transplantation will be significantly increased. Genetically modified stem cell transplantation has the potential application in a variety of clinical diseases, including myocardial infarction, but its long-term safety remains to be further studied.