基因转染间充质干细胞的临床治疗:特点与问题  

Mesenchymal stem cells in gene therapy: specialty and problems

作　　者：李丽春 李剑平 

机构地区：[1]辽宁省血液中心,辽宁省沈阳市110044

出　　处：《中国组织工程研究》2014年第14期2257-2262,共6页Chinese Journal of Tissue Engineering Research

基　　金：沈阳市科学技术计划项目(F10-206-1-00)~~

摘　　要：背景:骨髓间充质干细胞因制备较易、具备有较强的自我增殖能力、稳定的生物学性状、低免疫原性、能在宿主脑中生存较长时间、易于转染外源性基因且有较高的转染率、对肿瘤细胞具有趋向性而成为一种较有希望的基因治疗的靶细胞。目的:利用不同基因转移的方法分析间充质干细胞用于临床多种难治性疾病基因治疗的优势和缺陷。方法:应用计算机检索2000年1月至2013年12月PubMed数据库、中国期刊全文数据库、万方数据库相关间充质干细胞的文章,中文检索词为"间充质干细胞,基因治疗",英文检索词为"mesenchymal stem cells,gene therapy"。共检索到文献2 114篇,最终纳入符合标准的42篇文献。结果与结论:基因治疗有多种,按基因操作分为:①基因修正和基因置换。②基因增强和基因失活。按靶细胞分为生殖细胞基因治疗和体细胞基因治疗。按给药途径分为活体外途径和活体内途径。相对与其他细胞骨髓间充质干细胞能在宿主脑中生存较长时间、易于转染外源性基因且有较高的转染率、对肿瘤细胞具有趋向性而成为一种较有希望的基因治疗的靶细胞。间充质干细胞作为基因治疗的载体其移植物抗宿主病、克隆氏病的治疗在国外已经进入到3期临床阶段。国内应用间充质干细胞治疗临床上一些难治性疾病也取得了明显的疗效。探索干细胞移植最佳治疗窗口,寻找适宜的基因剂量、移植细胞数量及合适的治疗时机,发挥最佳的治疗效果是有待解决的问题。BACKGROUND： Bone marrow mesenchymal stem cells have become a promising kind of target cells for gene therapy because of easy preparation, strong self-proliferative capacity, stable biological characteristics, low immunogenicity, long-term survival in the host brain, easy transfection by exogenous gene, high transfection efficiency, and tropism for tumor cells. OBJECTIVE： To analyze the advantages and disadvantages of mesenchymal stem cells used in gene therapy for refractory diseases based on different gene transfer methods. METHODS： A computer-based online retrieval was performed in PubMed database, Chinese Journal Full Text Database, Wanfang database to search papers regarding mesenchymal stem cells published from January 2000 to December 2013. The key words were ＂mesenchymal stem cell, gene therapy＂ in English and Chinese. Totally 2114 articles were retrieved, and finally, 42 articles were included in result analysis. RESULTS AND CONCLUSION： There are a variety of gene therapies that can be divided according to gene manipulation： （1） gene correction and gene replacement; （2） gene augmentation and gene inactivation. There are two routes of administration, in vitro and in vivo. As opposed to other cells, bone marrow mesenchymal stem cells can survive in the host brain for a longer time, are easier to be transfected by exogenous genes, and has a tropism for tumor cells. Thus, bone marrow mesenchymal stem cells have become a promising kind of target cells for gene therapy. Mesenchymal stem cell as carriers of the gene therapy have been used in phase III clinical trials for the treatment of graf{-versus-host disease and Crohn＇s disease treatment. In China, some achievements have been harvested in mesenchymal stem ceil therapy for refractory diseases. To exploring the optimal therapeutic window for stem cell transplantation, and to find the appropriate gene dosage, the number of transplanted cells and the appropriate timing of treatment are urgent to be solved.

关 键 词：骨髓间充质干细胞 临床治疗 基因转染 中国期刊全文数据库 体细胞基因治疗 移植物抗宿主病 GENETHERAPY 外源性基因 

分 类 号：R318[医药卫生—生物医学工程]