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间充质干细胞衍生的线粒体移植减轻缺血再灌注诱导的损伤,消除缺血再灌注诱导的细胞凋亡,恢复急性缺血性脑卒中大鼠模型的运动功能。

Mesenchymal stem cells-derived mitochondria transplantation mitigates I/R-induced injury, abolishes I/R-induced apoptosis, and restores motor function in acute ischemia stroke rat model.

机构信息

Medical Biotechnology Department, Paramedicine Faculty, Guilan University of Medical Sciences, Rasht, Iran.

Medical Biotechnology Department, Paramedicine Faculty, Guilan University of Medical Sciences, Rasht, Iran; Anatomical Sciences Department, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.

出版信息

Brain Res Bull. 2020 Dec;165:70-80. doi: 10.1016/j.brainresbull.2020.09.018. Epub 2020 Oct 1.

Abstract

Acute ischemia stroke (AIS) is one of the leading causes of mortality and disability worldwide, and its neurological impacts are devastating and permanent. There is no efficient and real treatment for acute ischemia stroke so far. Therefore, development of efficient therapeutic strategies is under focus of investigations by basic and clinical scientists. Brain is one of the organs with high energy consumption and metabolism. Hence, its functionality is highly dependent on mitochondrial activity and integrity. Therefore, mitochondria play a vital homeostatic role in neurons physiology and mitochondrial dysfunction implications have been reported in a variety of nervous system diseases including acute ischemia stroke. In an attempt to investigate and introduce a novel potential therapeutic strategy for AIS, we isolated healthy mitochondria from human umbilical cord derived mesenchymal stem cells (hUC-MSCs) followed by their intracerebroventricular transplantation in a rat model of ischemia, i.e. middle cerebral artery occlusion (MCAO). Here we report that the mitochondrial transplantation ameliorated the reperfusion/ischemia-induced damages as reflected by declined blood creatine phosphokinase level, abolished apoptosis, decreased astroglyosis and microglia activation, reduced infarct size, and improved motor function. Although further preclinical and clinical studies are required, our findings strongly suggest that transplantation of MSCs-derived mitochondria is a suitable, potential and efficient therapeutic option for acute ischemia stroke.

摘要

急性缺血性脑卒中(AIS)是全球范围内导致死亡和残疾的主要原因之一,其对神经系统的影响是毁灭性和永久性的。到目前为止,还没有有效的治疗急性缺血性脑卒中的方法。因此,基础和临床科学家都在关注开发有效的治疗策略。大脑是能量消耗和代谢水平较高的器官之一。因此,其功能高度依赖于线粒体的活性和完整性。因此,线粒体在神经元生理学中起着至关重要的稳态作用,线粒体功能障碍已在包括急性缺血性脑卒中在内的多种神经系统疾病中得到报道。为了研究和介绍一种治疗急性缺血性脑卒中的新的潜在治疗策略,我们从人脐带间充质干细胞(hUC-MSCs)中分离出健康的线粒体,然后将其移植到大脑中动脉闭塞(MCAO)的大鼠模型的侧脑室。结果显示,线粒体移植改善了再灌注/缺血引起的损伤,表现为血肌酸磷酸激酶水平下降、凋亡减少、星形胶质细胞和小胶质细胞激活减少、梗死体积减少以及运动功能改善。尽管还需要进一步的临床前和临床研究,但我们的研究结果强烈表明,MSC 来源的线粒体移植是治疗急性缺血性脑卒中的一种合适、有潜力和有效的治疗选择。

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