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静脉注射脂肪源性干细胞蛋白提取物可改善大鼠脑卒中模型的神经功能缺损。

Intravenous Administration of Adipose-Derived Stem Cell Protein Extracts Improves Neurological Deficits in a Rat Model of Stroke.

作者信息

Zhao Kai, Li Rui, Gu Changcong, Liu Long, Jia Yulong, Guo Xize, Zhang Wanping, Pei Chunying, Tian Linlu, Li Bo, Jia Jianrong, Cheng Huakun, Xu Hongwei, Li Lixian

机构信息

Department of Neurosurgery, The First Affiliate Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.

Neuroinflammation Unit, Montreal Neurological Institute, McGill University, Montreal, QC, Canada H3A 2B4.

出版信息

Stem Cells Int. 2017;2017:2153629. doi: 10.1155/2017/2153629. Epub 2017 Feb 7.

Abstract

Treatment of adipose-derived stem cell (ADSC) substantially improves the neurological deficits during stroke by reducing neuronal injury, limiting proinflammatory immune responses, and promoting neuronal repair, which makes ADSC-based therapy an attractive approach for treating stroke. However, the potential risk of tumorigenicity and low survival rate of the implanted cells limit the clinical use of ADSC. Cell-free extracts from ADSC (ADSC-E) may be a feasible approach that could overcome these limitations. Here, we aim to explore the potential usage of ADSC-E in treating rat transient middle cerebral artery occlusion (tMCAO). We demonstrated that intravenous (IV) injection of ADSC-E remarkably reduces the ischemic lesion and number of apoptotic neurons as compared to other control groups. Although ADSC and ADSC-E treatment results in a similar degree of a long-term clinical beneficial outcome, the dynamics between two ADSC-based therapies are different. While the injection of ADSC leads to a relatively mild but prolonged therapeutic effect, the administration of ADSC-E results in a fast and pronounced clinical improvement which was associated with a unique change in the molecular signature suggesting that potential mechanisms underlying different therapeutic approach may be different. Together these data provide translational evidence for using protein extracts from ADSC for treating stroke.

摘要

脂肪来源干细胞(ADSC)治疗通过减少神经元损伤、限制促炎免疫反应和促进神经元修复,显著改善中风后的神经功能缺损,这使得基于ADSC的治疗成为治疗中风的一种有吸引力的方法。然而,植入细胞的潜在致瘤风险和低存活率限制了ADSC的临床应用。ADSC的无细胞提取物(ADSC-E)可能是一种可以克服这些限制的可行方法。在此,我们旨在探索ADSC-E在治疗大鼠短暂性大脑中动脉闭塞(tMCAO)中的潜在用途。我们证明,与其他对照组相比,静脉注射ADSC-E可显著减少缺血性损伤和凋亡神经元的数量。尽管ADSC和ADSC-E治疗产生的长期临床有益效果程度相似,但两种基于ADSC的治疗方法之间的动态变化不同。虽然注射ADSC会导致相对温和但持续时间较长的治疗效果,但给予ADSC-E会导致快速且明显的临床改善,这与分子特征的独特变化有关,表明不同治疗方法的潜在机制可能不同。这些数据共同为使用ADSC的蛋白质提取物治疗中风提供了转化证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71fd/5318632/ff9329196a82/SCI2017-2153629.001.jpg

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