Department of Neurology, Medical Faculty, Heinrich-Heine-University, D-40225 Düsseldorf, Germany.
Int J Mol Sci. 2019 Jan 21;20(2):455. doi: 10.3390/ijms20020455.
The adult mammalian central nervous system (CNS) is generally considered as repair restricted organ with limited capacities to regenerate lost cells and to successfully integrate them into damaged nerve tracts. Despite the presence of endogenous immature cell types that can be activated upon injury or in disease cell replacement generally remains insufficient, undirected, or lost cell types are not properly generated. This limitation also accounts for the myelin repair capacity that still constitutes the default regenerative activity at least in inflammatory demyelinating conditions. Ever since the discovery of endogenous neural stem cells (NSCs) residing within specific niches of the adult brain, as well as the description of procedures to either isolate and propagate or artificially induce NSCs from various origins ex vivo, the field has been rejuvenated. Various sources of NSCs have been investigated and applied in current neuropathological paradigms aiming at the replacement of lost cells and the restoration of functionality based on successful integration. Whereas directing and supporting stem cells residing in brain niches constitutes one possible approach many investigations addressed their potential upon transplantation. Given the heterogeneity of these studies related to the nature of grafted cells, the local CNS environment, and applied implantation procedures we here set out to review and compare their applied protocols in order to evaluate rate-limiting parameters. Based on our compilation, we conclude that in healthy CNS tissue region specific cues dominate cell fate decisions. However, although increasing evidence points to the capacity of transplanted NSCs to reflect the regenerative need of an injury environment, a still heterogenic picture emerges when analyzing transplantation outcomes in injury or disease models. These are likely due to methodological differences despite preserved injury environments. Based on this meta-analysis, we suggest future NSC transplantation experiments to be conducted in a more comparable way to previous studies and that subsequent analyses must emphasize regional heterogeneity such as accounting for differences in gray versus white matter.
成年哺乳动物中枢神经系统（CNS）通常被认为是修复受限的器官，其再生丢失细胞并将其成功整合到受损神经束中的能力有限。尽管存在可以在受伤或疾病时被激活的内源性未成熟细胞类型，但细胞替代通常仍然不足、无定向或丢失的细胞类型无法正常产生。这种限制也解释了髓鞘修复能力，它至少在炎症性脱髓鞘疾病中仍然构成默认的再生活动。自从发现存在于成年大脑特定部位的内源性神经干细胞（NSC）以来，以及描述了从各种来源分离和增殖或人工诱导 NSC 的方法以来，该领域已经复兴。已经研究和应用了各种 NSC 来源，以基于成功整合来替代丢失的细胞并恢复功能。虽然指导和支持驻留在脑龛中的干细胞是一种可能的方法，但许多研究都探讨了它们在移植后的潜力。鉴于这些研究与移植细胞的性质、局部中枢神经系统环境和应用的植入程序的异质性，我们在此旨在回顾和比较它们的应用方案，以评估限速参数。基于我们的编译，我们得出结论，在健康的中枢神经系统组织中，区域特异性线索主导着细胞命运决定。然而，尽管越来越多的证据表明移植的 NSC 能够反映损伤环境的再生需求，但在分析损伤或疾病模型中的移植结果时，仍然出现异质化的情况。这可能是由于尽管保留了损伤环境，但方法学上的差异所致。基于这项荟萃分析，我们建议未来的 NSC 移植实验以更类似于以前研究的方式进行，并且随后的分析必须强调区域异质性，例如考虑灰质与白质的差异。
