Translational Platform for Regenerative Medicine, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland.
Cells. 2022 Apr 26;11(9):1464. doi: 10.3390/cells11091464.
Rapid developments in stem cell research in recent years have provided a solid foundation for their use in medicine. Over the last few years, hundreds of clinical trials have been initiated in a wide panel of indications. Disorders and injuries of the nervous system still remain a challenge for the regenerative medicine. Neural stem cells (NSCs) are the optimal cells for the central nervous system restoration as they can differentiate into mature cells and, most importantly, functional neurons and glial cells. However, their application is limited by multiple factors such as difficult access to source material, limited cells number, problematic, long and expensive cultivation in vitro, and ethical considerations. On the other hand, according to the available clinical databases, most of the registered clinical trials involving cell therapies were carried out with the use of mesenchymal stem/stromal/signalling cells (MSCs) obtained from afterbirth or adult human somatic tissues. MSCs are the multipotent cells which can also differentiate into neuron-like and glia-like cells under proper conditions in vitro; however, their main therapeutic effect is more associated with secretory and supportive properties. MSCs, as a natural component of cell niche, affect the environment through immunomodulation as well as through the secretion of the trophic factors. In this review, we discuss various therapeutic strategies and activated mechanisms related to bilateral MSC-NSC interactions, differentiation of MSCs towards the neural cells (subpopulation of crest-derived cells) under the environmental conditions, bioscaffolds, or co-culture with NSCs by recreating the conditions of the neural cell niche.
近年来,干细胞研究的快速发展为其在医学中的应用提供了坚实的基础。在过去的几年中,已经启动了数百项临床试验,涵盖了广泛的适应症。神经系统的疾病和损伤仍然是再生医学的一个挑战。神经干细胞(NSCs)是中枢神经系统修复的最佳细胞,因为它们可以分化为成熟细胞,最重要的是,可以分化为功能性神经元和神经胶质细胞。然而,它们的应用受到多种因素的限制,例如难以获得源材料、细胞数量有限、体外培养困难、时间长且昂贵,以及伦理考虑。另一方面,根据现有的临床数据库,大多数涉及细胞疗法的已注册临床试验都是使用从胎盘中或成人体组织中获得的间充质干细胞/基质/信号细胞(MSCs)进行的。MSCs 是多能细胞,在适当的体外条件下也可以分化为神经元样和神经胶质样细胞;然而,它们的主要治疗效果更多地与分泌和支持特性有关。MSCs 作为细胞龛的天然组成部分,通过免疫调节以及通过分泌营养因子来影响环境。在这篇综述中,我们讨论了与 MSC-NSC 相互作用、MSCs 在环境条件下向神经细胞(嵴源性细胞亚群)分化、生物支架或与 NSCs 共培养相关的各种治疗策略和激活机制,通过重建神经细胞龛的条件来实现。