组织工程血管化基因治疗的研究进展  

Research progress of gene therapy for vascularization of tissue engineering

作　　者：李光照 陈锐 贾洪林 任利玲[1] Li Guangzhao;Chen Rui;Jia Honglin;Ren Liling(School of Stomatology,Lanzhou University,Lanzhou 730000,Gansu Province,China)

机构地区：[1]兰州大学口腔医学院,甘肃省兰州市730000

出　　处：《中国组织工程研究》2022年第28期4569-4574,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金资助项目(81670969),项目参与者:任利玲;国家自然科学基金资助项目(81300860),项目负责人:任利玲;甘肃省自然科学基金(17JR5RA202),项目负责人:任利玲。

摘　　要：背景:在大块工程化移植物内部迅速形成功能性血管系统,是其在宿主体内成功存活的基本前提。利用基因工程技术实现工程组织血管化具有治疗效果好、费用低、安全性高等优点,开展工程组织血管化基因治疗的相关研究对实现长期有效的组织修复有着重大意义。目的:综述目前组织工程血管化基因治疗的种子细胞、目的基因和基因载体的研究现状及存在的主要问题,以期进一步探讨基因治疗在组织工程血管化中的应用前景。方法:在PubMed、Web of Science、CNKI上进行了文献检索,并以“Tissue engineering;Vascularization;Gene therapy;Seed cells;Target genes;Vectors”作为英文检索词,以“组织工程;血管化;基因治疗;种子细胞;目的基因;载体”作为中文检索词,对最终纳入的61篇文献进行了归纳总结。结果与结论:间充质干细胞、血管内皮细胞及内皮祖细胞是组织工程血管化基因治疗中最具潜力的种子细胞,不仅具有良好的血管诱导性,而且有利于多种病毒和非病毒载体的导入及血管化目的基因的表达。血管内皮生长因子、血管生成素1、碱性成纤维细胞生长因子、骨形态发生蛋白2、缺氧诱导因子1α等血管化目的基因,主要通过双/多基因联合、成骨与成血管耦合及上游基因调控等方式在工程化移植物内部构建出高效、稳定的血管网络。由于不同的病毒和非病毒载体具有各自的优缺点,因此在应用时主要根据基因转染效率、生物安全性、成本等方面来选择合适的载体。目前,尽管基因治疗在组织工程血管化中的应用研究已取得很大进展,但是要真正应用于临床实践,还需要突破众多技术瓶颈,例如如何提高目的因子的释放靶向性和降低安全风险等,这也是未来组织工程血管化基因治疗的研究方向和热点。BACKGROUND:The rapid formation of functional vascular system in large-scale engineered graft is the basic prerequisite for its successful survival in the host.The vascularization of tissue engineering by genetic engineering technology has the advantages of good therapeutic effect,low cost and high safety.It is of great significance to carry out the research on gene therapy for vascularization of tissue engineering for long-term effective tissue repair.OBJECTIVE:To summarize the current research status and main problems of seed cells,target genes and gene vectors of gene therapy in tissue engineering vascularization so as to further explore the application prospect of gene therapy in tissue engineering vascularization,.METHODS:The literature retrieval was conducted on PubMed,Web of Science,and CNKI with the key words of“tissue engineering;vascularization;gene therapy;seed cells;target genes;vectors”in Chinese and English,and 61 articles closely related to this study were selected for the review.RESULTS AND CONCLUSION:Mesenchymal stem cells,vascular endothelial cells and endothelial progenitor cells are the most potential seed cells for vascularization of tissue engineering using gene therapy.They not only have good vascular induction,but also benefit the introduction of many virus and non-viral vectors and the expression of vascularization target genes.Vascular endothelial growth factor,angiopoietin-1,basic fibroblast growth factor,bone morphogenetic protein-2,hypoxia inducible factor-1αand other vascularization target genes are mainly used to construct efficient and stable vascular network in engineering grafts by means of combination of double/multiple gene,coupling of osteogenesis and angiogenesis,and regulation of upstream gene.Since different viral and non-viral vectors have their own advantages and disadvantages,suitable vectors should be selected according to the efficiency of gene transfection,biological safety,and cost in application.At present,although great progress has been made in the application

关 键 词：组织工程 血管化 基因治疗 种子细胞 目的基因 载体 综述 

分 类 号：R459.9[医药卫生—治疗学] R318.08[医药卫生—临床医学]