Department of Surgery and Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 4N1, Canada.
Int J Mol Sci. 2023 Feb 8;24(4):3370. doi: 10.3390/ijms24043370.
Pluripotent neural stem or progenitor cells (NSC/NPC) have been reported in the brains of adult preclinical models for decades, as have mesenchymal stem/stromal cells (MSC) been reported in a variety of tissues from adults. Based on their in vitro capabilities, these cell types have been used extensively in attempts to repair/regenerate brain and connective tissues, respectively. In addition, MSC have also been used in attempts to repair compromised brain centres. However, success in treating chronic neural degenerative conditions such as Alzheimer's disease, Parkinson's disease, and others with NSC/NPC has been limited, as have the use of MSC in the treatment of chronic osteoarthritis, a condition affecting millions of individuals. However, connective tissues are likely less complex than neural tissues regarding cell organization and regulatory integration, but some insights have been gleaned from the studies regarding connective tissue healing with MSC that may inform studies attempting to initiate repair and regeneration of neural tissues compromised acutely or chronically by trauma or disease. This review will discuss the similarities and differences in the applications of NSC/NPC and MSC, where some lessons have been learned, and potential approaches that could be used going forward to enhance progress in the application of cellular therapy to facilitate repair and regeneration of complex structures in the brain. In particular, variables that may need to be controlled to enhance success are discussed, as are different approaches such as the use of extracellular vesicles from stem/progenitor cells that could be used to stimulate endogenous cells to repair the tissues rather than consider cell replacement as the primary option. Caveats to all these efforts relate to whether cellular repair initiatives will have long-term success if the initiators for neural diseases are not controlled, and whether such cellular initiatives will have long-term success in a subset of patients if the neural diseases are heterogeneous and have multiple etiologies.
多能神经干细胞或祖细胞 (NSC/NPC) 在数十年前的临床前动物模型大脑中被报道，间充质干细胞/基质细胞 (MSC) 在成年各种组织中也被报道。基于其体外能力，这些细胞类型已被广泛用于试图分别修复/再生大脑和结缔组织。此外，MSC 也被用于试图修复受损的大脑中心。然而，用 NSC/NPC 治疗慢性神经退行性疾病（如阿尔茨海默病、帕金森病等）的成功有限，用 MSC 治疗影响数百万人的慢性骨关节炎的成功也有限。然而，与神经组织相比，结缔组织在细胞组织和调节整合方面可能不太复杂，但从 MSC 治疗结缔组织愈合的研究中已经获得了一些见解，这些见解可能为试图启动急性或慢性创伤或疾病引起的神经组织修复和再生的研究提供信息。本综述将讨论 NSC/NPC 和 MSC 的应用中的相似性和差异，从中吸取了一些经验教训，并探讨了潜在的方法，这些方法可以在未来用于增强细胞疗法的应用，以促进大脑复杂结构的修复和再生。特别是，讨论了可能需要控制哪些变量以提高成功率，以及不同的方法，例如使用干细胞/祖细胞的细胞外囊泡，这些方法可以用来刺激内源性细胞修复组织，而不是将细胞替代作为主要选择。所有这些努力都存在一个问题，即如果不控制神经疾病的启动因素，细胞修复计划是否会长期成功，以及如果神经疾病具有异质性且具有多种病因，那么这些细胞计划是否会在一部分患者中取得长期成功。
