Student Research Committee, Babol University of Medical Sciences, Babol, Iran.
Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
J Cell Physiol. 2020 Mar;235(3):2023-2036. doi: 10.1002/jcp.29195. Epub 2019 Sep 15.
Oligodendrocyte precursor cells (OPCs) are considered as the main cell source for myelination in the central nervous system. Following demyelination, proliferation, migration, and differentiation capability of endogenous OPCs remarkably increase leading to remyelination in damaged areas. Despite the beneficial impacts of resident OPCs for myelin repair, the capacity of endogenous repair is low and insufficient. Therefore, several strategies have been developed to improve endogenous myelin repair. Although stem cell therapy has been introduced as a promising strategy for neurodegenerative disorders, but several limitations such as cell rejection, teratoma formation, and ethical concerns have hampered the extensive application of stem cells in clinic. In recent years, direct conversion of fully differentiated somatic cells into desired cells in the lesion area has opened a new era in regenerative medicine. In addition to direct reprogramming of somatic cells to neurons, recent evidence have also demonstrated that somatic cells, including fibroblasts and astrocytes, can be directly reprogrammed to OPC-like cells by overexpression of some specific transcription factors, microRNAs, or application of small molecules. Interestingly, induced OPCs differentiated to myelinating oligodendrocytes that could effectively ensheath the host axons. In the present review article, the current advancements in direct conversion of somatic cells towards oligodendroglial cells have been discussed both in vitro and in vivo.
少突胶质前体细胞(OPC)被认为是中枢神经系统髓鞘形成的主要细胞来源。脱髓鞘后,内源性 OPC 的增殖、迁移和分化能力显著增强,导致损伤部位的髓鞘再生。尽管内源性 OPC 对髓鞘修复有有益影响,但内源性修复能力较低且不足。因此,已经开发了几种策略来提高内源性髓鞘修复能力。尽管干细胞疗法已被引入作为神经退行性疾病的一种有前途的策略,但细胞排斥、畸胎瘤形成和伦理问题等几个限制因素阻碍了干细胞在临床上的广泛应用。近年来,将完全分化的体细胞直接转化为病变区域所需的细胞,为再生医学开辟了一个新时代。除了直接将体细胞重编程为神经元外,最近的证据还表明,包括成纤维细胞和星形胶质细胞在内的体细胞可以通过过表达某些特定的转录因子、microRNAs 或应用小分子直接重编程为 OPC 样细胞。有趣的是,诱导的 OPC 分化为髓鞘形成的少突胶质细胞,可有效地包裹宿主轴突。在本文综述中,讨论了体外和体内直接将体细胞转化为少突胶质细胞的最新进展。