间质干细胞的基因治疗

Gene therapy based on mesenchymal stem cells

目的:总结以间质干细胞为载体细胞的基因治疗的进展,为细胞基因修饰在实验性基因治疗中的应用提供提示。资料来源:用计算机检索Medline,Pubmed和Springer数据库1998-01/2005-12与骨髓间质干细胞基因治疗相关的文章,检索词为“mesenchymalstemcells,genetherapy”,并限定文章语言种类为English。同时计算机搜索CNKI中国全文期刊数据库1998-01/2005-12与骨髓间质干细胞基因治疗相关的文章,限定文章语言种类为中文,检索词为“间质干细胞,基因治疗”。资料选择:对资料进行初审,纳入标准:①选择与间质干细胞,转基因,基因治疗、运输、转导有关文章。②在1998年以后发表的文章。排除标准:重复文章、综述文献、Meta分析类文章。资料提炼:共搜集到273篇相关文章,入选41篇。对检索到的文章的相关信息综合加以概括综述,其中间质干细胞的生物学特性、自我更新和分化10篇,以间质干细胞作为靶细胞的基因治疗31篇。资料综合:细胞介导的基因治疗,包括诱导转移性基因进入细胞的病毒和非病毒载体的设计,转移性基因的能力,引导修饰性基因或者被分泌的治疗性物质进入疾病组织的能力以及在干细胞内的治疗性物质产物的最佳化和调节等。运载缺失的基因可以促进心脏的功能性恢复,心肌的再生则可以用来修复心肌损伤。骨髓来源的间质干细胞对治疗自身免疫性疾病的免疫抑制效应非常重要。结论:间质干细胞是具有潜在应用前景的基因治疗的载体细胞。间质干细胞来源丰富,易于在体外分离和培养,并具有自我更新和多系分化的能力,通过体内外分泌一系列的蛋白从而对遗传缺陷性疾病或获得性疾病进行治疗。

OBJECTIVE： To summarize the advances in the gene therapy based on mesenchymal stem cells （MSCs）, so as to provide new ideas for application of gene modified ceils in gene therapy. DATA SOURCES： Using the key words of ＂mesenchymal stem cells, gene therapy＂, we searched the Medline, Pubmed and Springer databases for articles on gene therapy of MSCs published in English from January 1998 to December 2005, Meanwhile, we retrieved the CNKI database for related articles on gene therapy of MSCs published in Chinese from January 1998 to December 2005 with the same key words in Chinese. STUDY SELECTION： All articles were selected firstly. Inclusive criteria： （1）Articles on MSCs, transgene, gene therapy, transduetion and delivery. （2）Articles published after 1998. Exclusive criteria： Repeated study, review articles and Meta analytical papers. DATA EXTRACTION： Among 273 selected articles, 41 articles were included, All relevant information of the selected articles were summarized, including 10 articles on biological characteristics, self renewal and differentiation, and 31 articles on gene therapy with MSCs as target cells. DATA SYNTHESIS： Cell-based gene therapy including the design of inducing the metastatic gene into cellular viral and non-viral vectors, ability of metastatic gene, the ability of modified gene or secreted therapeutic matters into disease tissue, and refine and regulation of products of therapeutic matters in stem cells. Carrying deleting gene can improve the functional recovery of heart, and the myocardial regeneration can repair myocardial injury. Marrow-derived MSCs play important roles in treating immune suppression of autoimmune disease. CONCLUSION： MSCs are vector cells for potential cell-based gene therapy. MSCs have rich sources, and easy to isolate and culture in vivo. MSCs retain the ability of self-renewal and differentiation into various types of tissue ceils, and can be engineered to secrete a series of different proteins in vivo and ex vivo that can potentially treat a variety of inherited and acquired diseases.