Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku 812-8582, Fukuoka, Japan.
Cells. 2021 May 10;10(5):1145. doi: 10.3390/cells10051145.
Tissue-specific stem cells give rise to new functional cells to maintain tissue homeostasis and restore damaged tissue after injury. To ensure proper brain functions in the adult brain, neural stem cells (NSCs) continuously generate newborn neurons that integrate into pre-existing neuronal networks. Proliferation, as well as neurogenesis of NSCs, are exquisitely controlled by extrinsic and intrinsic factors, and their underlying mechanisms have been extensively studied with the goal of enhancing the neurogenic capacity of NSCs for regenerative medicine. However, neurogenesis of endogenous NSCs alone is insufficient to completely repair brains damaged by neurodegenerative diseases and/or injury because neurogenic areas are limited and few neurons are produced in the adult brain. An innovative approach towards replacing damaged neurons is to induce conversion of non-neuronal cells residing in injured sites into neurons by a process referred to as direct reprogramming. This review describes extrinsic and intrinsic factors controlling NSCs and neurogenesis in the adult brain and discusses prospects for their applications. It also describes direct neuronal reprogramming technology holding promise for future clinical applications.
组织特异性干细胞产生新的功能细胞，以维持组织内稳态并在损伤后修复受损组织。为了确保成年大脑的正常功能，神经干细胞 (NSC) 持续产生新的神经元，这些神经元整合到预先存在的神经网络中。NSC 的增殖和神经发生受到外在和内在因素的精细调控，其潜在机制已被广泛研究，目的是增强 NSCs 的神经发生能力，用于再生医学。然而，内源性 NSCs 的神经发生本身不足以完全修复由神经退行性疾病和/或损伤引起的大脑损伤，因为神经发生区域有限，成年大脑中产生的神经元数量很少。一种替代受损神经元的创新方法是通过一种称为直接重编程的过程，诱导驻留在损伤部位的非神经元细胞转化为神经元。本综述描述了控制成年大脑中 NSCs 和神经发生的外在和内在因素，并讨论了它们的应用前景。它还描述了具有未来临床应用前景的直接神经元重编程技术。
