Department of Molecular Biology, The University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, The University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA; Department of Physical Therapy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Prog Neurobiol. 2017 Oct;157:212-229. doi: 10.1016/j.pneurobio.2016.01.006. Epub 2016 Feb 1.
Neural cell identity reprogramming strategies aim to treat age-related neurodegenerative disorders with newly induced neurons that regenerate neural architecture and functional circuits in vivo. The isolation and neural differentiation of pluripotent embryonic stem cells provided the first in vitro models of human neurodegenerative disease. Investigation into the molecular mechanisms underlying stem cell pluripotency revealed that somatic cells could be reprogrammed to induced pluripotent stem cells (iPSCs) and these cells could be used to model Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, and Parkinson disease. Additional neural precursor and direct transdifferentiation strategies further enabled the induction of diverse neural linages and neuron subtypes both in vitro and in vivo. In this review, we highlight neural induction strategies that utilize stem cells, iPSCs, and lineage reprogramming to model or treat age-related neurodegenerative diseases, as well as, the clinical challenges related to neural transplantation and in vivo reprogramming strategies.
神经细胞身份重编程策略旨在利用新诱导的神经元来治疗与年龄相关的神经退行性疾病，这些神经元在体内再生神经结构和功能回路。多能胚胎干细胞的分离和神经分化为人类神经退行性疾病提供了第一个体外模型。对干细胞多能性的分子机制的研究表明，体细胞可以被重编程为诱导多能干细胞（iPSCs），这些细胞可用于模拟阿尔茨海默病、肌萎缩侧索硬化症、亨廷顿病和帕金森病。此外，神经前体细胞和直接转分化策略进一步使体外和体内诱导多种神经谱系和神经元亚型成为可能。在这篇综述中，我们重点介绍了利用干细胞、iPSCs 和谱系重编程来模拟或治疗与年龄相关的神经退行性疾病的神经诱导策略，以及与神经移植和体内重编程策略相关的临床挑战。
