Double-Injected Human Stem Cells Enhance Rehabilitation in TBI Mice Via Modulation of Survival and Inflammation.
Double-Injected Human Stem Cells Enhance Rehabilitation in TBI Mice Via Modulation of Survival and Inflammation.
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DOI：
10.1007/s12035-017-0683-3
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发表时间：
2018-06
影响因子：
5.1
通讯作者：
Moon J
中科院分区：
文献类型：
--
作者：
Kim C;Park JM;Kong T;Lee S;Seo KW;Choi Y;Song YS;Moon J
创伤性脑损伤（TBI）是一种复杂的脑损伤形式，是成人死亡的主要原因。在机械和结构性一次损伤后，一系列二次损伤，包括神经递质介导的细胞毒性、钙和大分子稳态失调以及氧化应激增加，加剧了脑损伤和功能缺陷。虽然干细胞疗法被认为是脑损伤（如TBI和中风）的替代疗法，但仍存在许多障碍。特别是，用药物或干细胞治疗TBI的时间窗口及其疗效仍然模糊。人胎盘来源的间充质干细胞（hpMSCs）在干细胞治疗中受到了广泛的关注，因为它们可以大量获得而没有伦理问题，并且因为它们的免疫调节能力和在几种疾病中的有效性，例如阿尔茨海默病和中风。在这里，我们用动物模型测试了hpMSC用于TBI治疗的可行性，并试图确定细胞治疗的适当时间点。在损伤后4和24小时进行两次注射显著减少了梗死面积，并抑制了损伤周围的星形胶质细胞和小胶质细胞活化。随着损伤的减少，双重注射小鼠显示出增强的抗炎和TNF-α受体2（TNFR 2）相关的生存信号，并抑制促炎和氧化反应。此外，双重治疗的TBI小鼠表现出恢复的感觉运动功能，并减少受损区域周围神经毒性Aβ42斑块的形成。在这项研究中，我们显示了hpMSCs的扩展治疗潜力，并得出结论，在适当的时间窗口内治疗对TBI恢复至关重要。
Traumatic brain injury (TBI), a complicated form of brain damage, is a major cause of mortality in adults. Following mechanical and structural primary insults, a battery of secondary insults, including neurotransmitter-mediated cytotoxicity, dysregulation of calcium and macromolecule homeostasis, and increased oxidative stress, exacerbate brain injury and functional deficits. Although stem cell therapy is considered to be an alternative treatment for brain injuries, such as TBI and stroke, many obstacles remain. In particular, the time window for TBI treatment with either drugs or stem cells and their efficacy is still vague. Human placenta-derived mesenchymal stem cells (hpMSCs) have received extensive attention in stem cell therapy because they can be acquired in large numbers without ethical issues and because of their immune-modulating capacity and effectiveness in several diseases, such as Alzheimer’s disease and stroke. Here, we tested the feasibility of hpMSCs for TBI treatment with an animal model and attempted to identify appropriate time points for cell treatments. Double injections at 4 and 24 h post-injury significantly reduced the infarct size and suppressed astrocyte and microglial activation around the injury. With reduced damage, double-injected mice showed enhanced anti-inflammatory- and TNF-α receptor 2 (TNFR2)-associated survival signals and suppressed pro-inflammatory and oxidative responses. In addition, double-treated TBI mice displayed restored sensory motor functions and reduced neurotoxic Aβ42 plaque formation around the damaged areas. In this study, we showed the extended therapeutic potentials of hpMSCs and concluded that treatment within an appropriate time window is critical for TBI recovery.
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