Stem Cell Reviews and Reports ( IF 4.5 ) Pub Date : 2021-08-11 , DOI: 10.1007/s12015-021-10213-y Catherine Brégère 1 , Bernd Schwendele 1 , Boris Radanovic 1 , Raphael Guzman 1
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Neonatal hypoxia-ischemia encephalopathy (HIE) refers to a brain injury in term infants that can lead to death or lifelong neurological deficits such as cerebral palsy (CP). The pathogenesis of this disease involves multiple cellular and molecular events, notably a neuroinflammatory response driven partly by microglia, the brain resident macrophages. Treatment options are currently very limited, but stem cell (SC) therapy holds promise, as beneficial outcomes are reported in animal studies and to a lesser degree in human trials. Among putative mechanisms of action, immunomodulation is considered a major contributor to SC associated benefits. The goal of this review is to examine whether microglia is a cellular target of SC-mediated immunomodulation and whether the recruitment of microglia is linked to brain repair. We will first provide an overview on microglial activation in the rodent model of neonatal HI, and highlight its sensitivity to developmental age. Two complementary questions are then addressed: (i) do immune-related treatments impact microglia and provide neuroprotection, (ii) does stem cell treatment modulates microglia? Finally, the immune-related findings in patients enrolled in SC based clinical trials are discussed. Our review points to an impact of SCs on the microglial phenotype, but heterogeneity in experimental designs and methodological limitations hamper our understanding of a potential contribution of microglia to SC associated benefits. Thorough analyses of the microglial phenotype are warranted to better address the relevance of the neuroimmune crosstalk in brain repair and improve or advance the development of SC protocols in humans.
Graphical abstract
中文翻译：
新生儿缺氧缺血后小胶质细胞和干细胞介导的神经保护
新生儿缺氧缺血性脑病（HIE）是指足月儿的脑损伤，可导致死亡或终生神经功能缺陷，例如脑瘫（CP）。这种疾病的发病机制涉及多种细胞和分子事件，特别是部分由小胶质细胞（大脑常驻巨噬细胞）驱动的神经炎症反应。目前的治疗选择非常有限，但干细胞 (SC) 疗法大有希望，因为动物研究中报告了有益的结果，而人体试验中也报告了较小程度的有益结果。在假定的作用机制中，免疫调节被认为是 SC 相关益处的主要贡献者。本综述的目的是检查小胶质细胞是否是 SC 介导的免疫调节的细胞靶标，以及小胶质细胞的募集是否与脑修复有关。我们将首先概述新生儿 HI 啮齿动物模型中小胶质细胞的激活，并强调其对发育年龄的敏感性。然后解决两个互补的问题：（i）免疫相关治疗是否影响小胶质细胞并提供神经保护，（ii）干细胞治疗是否调节小胶质细胞？最后，讨论了参加 SC 临床试验的患者的免疫相关发现。我们的综述指出了 SC 对小胶质细胞表型的影响，但实验设计的异质性和方法学限制阻碍了我们对小胶质细胞对 SC 相关益处的潜在贡献的理解。有必要对小胶质细胞表型进行彻底分析，以更好地解决神经免疫串扰在大脑修复中的相关性，并改善或推进人类 SC 方案的开发。
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