Department of Neurosurgery, Hyogo College of Medicine, Hyogo 663-8501, Japan.
Laboratory of Neurogenesis and CNS Repair, Hyōgo College of Medicine, Hyogo 663-8501, Japan; General Education Center, Hyogo University of Health Science, Hyogo 650-8530, Japan.
Brain Res. 2019 May 15;1711:58-67. doi: 10.1016/j.brainres.2018.12.042. Epub 2019 Jan 4.
Even today, intracerebral hemorrhage (ICH) is a major cause of death and disabilities. Rehabilitation is preferentially applied for functional recovery although its effect is limited. Recent studies have suggested that intravenous administration of mesenchymal stem cells would improve the post-ICH neurological deficits. Human adipose-derived stem cells (hADSCs) have been established in our laboratory. We aimed to evaluate the therapeutic efficacy of the hADSCs on the post-ICH neurological deficits using a clinical-relevant ICH mouse model. We also evaluated immune responses to clarify the underlying mechanisms. The hADSCs expressed MSC markers at high levels. The hADSCs administration into the ICH-bearing mice improved the neurological deficits during the subacute phases, which was shown by neurobehavioral experiments. Besides, the hADSC administration decreased the number of CD11CD45 cells and increased the proportion of CD86 and Ly6C cells in the ICH lesions. In summary, intravenous administration of hADSCs during the acute phase improved ICH-induced neurological deficits during the subacute phase because of the suppression of acute inflammation mediated by CD11CD45 subpopulations. Our data suggest that hADSCs can be served as a novel strategy for ICH treatment.
即使在今天，脑出血（ICH）仍是主要的死亡和致残原因之一。尽管康复治疗的效果有限，但它仍是首选的功能恢复方法。最近的研究表明，静脉内给予间充质干细胞可改善脑出血后的神经功能缺损。我们实验室已经建立了人脂肪来源的干细胞（hADSCs）。我们旨在使用与临床相关的脑出血小鼠模型来评估 hADSCs 对脑出血后神经功能缺损的治疗效果。我们还评估了免疫反应，以阐明其潜在机制。hADSCs 高表达 MSC 标志物。hADSCs 给药到脑出血小鼠模型中可改善亚急性期的神经功能缺损，这可通过神经行为学实验证实。此外，hADSC 给药可减少 ICH 病变中的 CD11CD45 细胞数量，并增加 CD86 和 Ly6C 细胞的比例。综上所述，在急性期静脉内给予 hADSCs 可通过抑制 CD11CD45 亚群介导的急性炎症来改善脑出血引起的亚急性期神经功能缺损。我们的数据表明，hADSCs 可作为脑出血治疗的一种新策略。
