线粒体移植疗法

Mitochondrial Transplantation Therapy

线粒体移植(mitochondrial transplantation)曾指利用显微操作,将分离获得的正常线粒体注射到卵细胞的辅助生殖技术。近年兴起的,将线粒体直接注射到组织器官的受损部位,或注射到血液循环系统,进而发挥治疗作用的技术,同样被称为线粒体移植。在细胞研究水平,则是直接将线粒体与培养细胞共同孵育。这些技术方法也统称为线粒体疗法。该文系统综述了线粒体移植在心、脑、肝、肾、肺、骨骼肌等多种组织器官损伤模型中,在小鼠、大鼠、兔、猪等多种实验动物模型中的研究成果,以及在心脏病患儿体内的初步临床研究成果;介绍了学界提出的线粒体进入细胞、产生ATP等作用机制,及对此机制的相关质疑;同时介绍了自己课题组关于线粒体移植治疗皮肤急性光损伤和烧伤的研究成果,提出并讨论了线粒体可能不需要进入细胞即可发挥作用的假说。该文提出线粒体移植机制的内化机制和非内化机制概念,为深化线粒体移植机制研究指出新方向。

Mitochondrial transplantation was ever referred to the assisted reproductive technology that in­jects isolated normal mitochondria into oocytes using micromanipulation.While,in the recent years,the technique of injecting healthy mitochondria directly into damaged tissues or organs,or injecting into the blood circulation,and subsequently exerting a therapeutic effect is also named as mitochondrial transplantation.In the cultured cell models,mitochondria are directly incubated with cells.This technique can also be termed as mitochondrial therapy.In the present review,the mitochondrial transplantation in diverse tissue and organ injury models,including but not limited to heart,brain,liver,kidney,lung,and skeletal muscle,in experimental animal models such as mice,rats,rabbits,and pigs,as well as preliminary clinical studies conducted on children with heart diseases are introduced.The proposed internalization mechanism,which is mitochondria entering cells to produce ATP,and its limitations are also introduced and discussed.Finally,a hypothesis that mitochondria may not need to enter the cell to function is proposed and named as non-internalization mechanism corresponding to the former internalization mechanism.This review puts forward a new direction for deepening the study of mitochondrial transplantation and the related mechanisms.