Tang Xiangwen, Deng Peng, Li Lin, He Yuqing, Wang Jinchao, Hao Dingjun, Yang Hao
Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China.
Basic Medical School Academy, Shaanxi University of Chinese Medicine, Xianyang, 712046, China.
Stem Cell Res Ther. 2024 Dec 18;15(1):482. doi: 10.1186/s13287-024-04089-1.
Neural stem cells (NSCs) have increasingly been recognized as the most promising candidates for cell-based therapies for the central nervous system (CNS) injuries, primarily due to their pluripotent differentiation capabilities, as well as their remarkable secretory and homing properties. In recent years, extensive research efforts have been initiated to explore the therapeutic potential of NSC transplantation for CNS injuries, yielding significant advancements. Nevertheless, owing to the formation of adverse microenvironment at post-injury leading to suboptimal survival, differentiation, and integration within the host neural network of transplanted NSCs, NSC-based transplantation therapies often fall short of achieving optimal therapeutic outcomes. To address this challenge, genetic modification has been developed an attractive strategy to improve the outcomes of NSC therapies. This is mainly attributed to its potential to not only enhance the differentiation capacity of NSCs but also to boost a range of biological activities, such as the secretion of bioactive factors, anti-inflammatory effects, anti-apoptotic properties, immunomodulation, antioxidative functions, and angiogenesis. Furthermore, genetic modification empowers NSCs to play a more robust neuroprotective role in the context of nerve injury. In this review, we will provide an overview of recent advances in the roles and mechanisms of NSCs genetically modified with various therapeutic genes in the treatment of neural injuries and neural disorders. Also, an update on current technical parameters suitable for NSC transplantation and functional recovery in clinical studies are summarized.
神经干细胞（NSCs）越来越被认为是中枢神经系统（CNS）损伤基于细胞治疗最有前景的候选者，主要是由于其多能分化能力以及显著的分泌和归巢特性。近年来，人们已经开展了广泛的研究工作来探索NSC移植治疗CNS损伤的潜力，并取得了重大进展。然而，由于损伤后不利微环境的形成，导致移植的NSCs在宿主神经网络中的存活、分化和整合不理想，基于NSC的移植治疗往往难以达到最佳治疗效果。为了应对这一挑战，基因修饰已成为一种有吸引力的策略来改善NSC治疗的效果。这主要归因于其不仅有可能增强NSCs的分化能力，还能促进一系列生物活性，如生物活性因子的分泌、抗炎作用、抗凋亡特性、免疫调节、抗氧化功能和血管生成。此外，基因修饰使NSCs在神经损伤的情况下发挥更强有力的神经保护作用。在这篇综述中，我们将概述用各种治疗性基因进行基因修饰的NSCs在治疗神经损伤和神经疾病中的作用及机制的最新进展。同时，总结了临床研究中适用于NSC移植和功能恢复的当前技术参数的最新情况。
