Neuroplasticity therapy using glia-like cells derived from human mesenchymal stem cells for the recovery of cerebral infarction sequelae.

IF 12.1 1区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Eun Ji Lee, Min-Ju Lee, Ye Jin Ryu, Sang-Hyeon Nam, Rokhyun Kim, Sehyeon Song, Kyunghyuk Park, Young Jun Park, Jong-Il Kim, Seong-Ho Koh, Mi-Sook Chang
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引用次数: 0

Abstract

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.

利用从人类间充质干细胞中提取的胶质样细胞进行神经可塑性强化治疗,以恢复脑梗塞后遗症。
尽管全球缺血性中风发病率急剧上升,但仍缺乏有效的疗法来减轻脑梗塞后遗症。本研究探讨了利用向胶质样细胞(ghMSCs)诱导的人类间充质干细胞(hMSCs)来改善脑梗塞导致的慢性后遗症。转录组分析表明,ghMSCs具有星形胶质细胞的特征,利用有机脑片培养进行的体内外评估表明,与hMSCs相比,ghMSCs对缺血性损伤具有更强的神经再生和神经保护活性。在使用 CXCR2 拮抗剂进行预处理后,观察到的 ghMSCs 的有益作用会减弱,这表明 CXCR2 信号传导起着直接作用。在脑梗塞大鼠身上进行的研究表明,在亚急性至慢性阶段移植ghMSCs,可恢复神经行为功能,并以剂量依赖的方式减少慢性脑梗塞。CXCR2拮抗剂也抑制了这些有益影响。分子分析证实,神经可塑性的增强有助于ghMSCs的神经再生作用。这些数据表明,ghMSCs有望通过增强神经可塑性来治疗脑梗塞导致的难治性后遗症,并确定CXCR2信号传导是ghMSCs作用机制的重要介质。
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来源期刊
Molecular Therapy
Molecular Therapy 医学-生物工程与应用微生物
CiteScore
19.20
自引率
3.20%
发文量
357
审稿时长
3 months
期刊介绍: Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.
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