INDUCTION OF RETINAL GANGLION-LIKE CELLS FROM FIBROBLASTS BY ADENOVIRAL GENE DELIVERY
INDUCTION OF RETINAL GANGLION-LIKE CELLS FROM FIBROBLASTS BY ADENOVIRAL GENE DELIVERY
复制标题
通过腺病毒基因递送从成纤维细胞诱导视网膜神经节样细胞
DOI：
10.1016/j.neuroscience.2013.07.001
复制
发表时间：
2013-10-10
期刊：
影响因子：
3.3
通讯作者：
Guo, W.
中科院分区：
文献类型：
--
作者：
Meng, F.;Wang, X.;Guo, W.
中枢神经系统神经元在出生后无法再生，这极大地阻碍了许多神经退行性疾病的有效治疗。从诱导多能干细胞分化而来的神经元被认为是基于细胞的疗法的可能选择。最近的发现表明，成纤维细胞可以直接转化为神经元，而无需经过多能状态的转变。这种方法可能成为神经退行性疾病细胞治疗更有效、更方便的方法。目前，多种类型的神经元已由成纤维细胞直接产生，包括多巴胺神经元、运动神经元和神经祖细胞。在我们的研究中，通过筛选一系列候选基因，我们发现腺病毒介导的Ascl1、Brn3b和Ngn2的转导可以直接将小鼠成纤维细胞转化为视网膜神经节样细胞。诱导的视网膜神经节样细胞共表达多种视网膜神经节细胞标记物，并表现出功能性神经元的膜特性。腺病毒介导的重编程比慢病毒介导的重编程发生得快得多。此外，通过腺病毒基因递送产生的诱导性视网膜神经节样细胞没有外源基因整合。腺病毒诱导的视网膜神经节样细胞在临床治疗中表现出巨大的潜在应用价值，为视网膜退行性疾病的研究提供了一个新的平台。 (c) 2013 年国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Central nervous system neurons fail to regenerate after birth, which greatly hampers the effective treatment of many neurodegenerative diseases. Neurons differentiated from induced pluripotent stem cells have been considered a possible option for cell-based therapies. Recent discoveries have revealed that fibroblasts can be directly converted into neurons without a transition through a pluripotent state. This approach might serve as a more efficient and convenient method for the cellular therapy of neurodegenerative diseases. Currently, several types of neurons have been directly generated from fibroblasts, including dopamine neurons, motor neurons and neural progenitor cells. In our study, by screening a series of candidate genes, we found that the adenovirus-mediated transduction of Ascl1, Brn3b and Ngn2 can directly convert mouse fibroblasts to retinal ganglion-like cells. The induced retinal ganglion-like cells co-express multiple retinal ganglion cell markers, and exhibit membrane properties of functional neurons. The reprogramming mediated by adenoviruses occurs much sooner than that mediated by lentiviruses. Furthermore, the induced retinal ganglion-like cells that are produced via adenoviral gene delivery are free of exogenous gene integration. Retinal ganglion-like cells that are induced by adenoviruses demonstrate great potential applicability in clinical therapy and provide a novel platform for the research of retinal degenerative diseases. (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.