Despite a dramatic increase in ischemic stroke incidence worldwide, effective therapies for attenuating sequelae of cerebral infarction are lacking. This study investigates the use of human mesenchymal stem cells (hMSCs) induced toward glia-like cells (ghMSCs) to ameliorate chronic sequelae resulting from cerebral infarction. Transcriptome analysis demonstrated that ghMSCs exhibited astrocytic characteristics, and assessments conducted ex vivo using organotypic brain slice cultures demonstrated that ghMSCs exhibited superior neuroregenerative and neuroprotective activity against ischemic damage compared to hMSCs. The observed beneficial effects of ghMSCs were diminished by pre-treatment with a CXCR2 antagonist, indicating a direct role for CXCR2 signaling. Studies conducted in rats subjected to cerebral infarction demonstrated that ghMSCs restored neurobehavioral functions and reduced chronic brain infarction in a dose-dependent manner when transplanted at the subacute-to-chronic phase. These beneficial impacts were also inhibited by a CXCR2 antagonist. Molecular analyses confirmed that increased neuroplasticity contributed to ghMSCs’ neuroregenerative effects. These data indicate that ghMSCs hold promise for treating refractory sequelae resulting from cerebral infarction by enhancing neuroplasticity and identify CXCR2 signaling as an important mediator of ghMSCs’ mechanism of action.

中文翻译：

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使用来自人间充质干细胞的神经胶质样细胞的神经可塑性增强疗法用于脑梗死后遗症的恢复


尽管全球缺血性卒中发病率急剧增加，但缺乏减轻脑梗死后遗症的有效疗法。本研究调查了使用诱导神经胶质样细胞 （ghMSC） 的人间充质干细胞 （hMSC） 来改善脑梗死引起的慢性后遗症。转录组分析表明 ghMSC 表现出星形胶质细胞特征，使用器官型脑切片培养物进行的离 体评估表明，与 hMSC 相比，ghMSC 表现出优异的神经再生和神经保护活性，对抗缺血性损伤。用 CXCR2 拮抗剂预处理后，观察到的 ghMSC 有益作用减弱，表明 CXCR2 信号传导的直接作用。在脑梗死大鼠中进行的研究表明，在亚急性至慢性期移植时，ghMSCs 以剂量依赖性方式恢复神经行为功能并减少慢性脑梗塞。这些有益影响也被 CXCR2 拮抗剂抑制。分子分析证实，神经可塑性增加有助于 ghMSC 的神经再生作用。这些数据表明，ghMSC 有望通过增强神经可塑性治疗脑梗死引起的难治性后遗症，并确定 CXCR2 信号转导是 ghMSC 作用机制的重要介质。