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表达碱性成纤维细胞生长因子的神经干细胞移植促进短暂性脑缺血大鼠脑内细胞迁移和功能恢复。

Transplantation of bFGF-expressing neural stem cells promotes cell migration and functional recovery in rat brain after transient ischemic stroke.

作者信息

Zhang Jin-Jing, Zhu Juan-Juan, Hu Yuan-Bo, Xiang Guang-Heng, Deng Lian-Cheng, Wu Fen-Zan, Wei Xiao-Jie, Wang Ying-Hao, Sun Liang-Yan, Lou Xiao-Qing, Shao Min-Min, Mao Mao, Zhang Hong-Yu, Xu Yue-Ping, Zhu Si-Pin, Xiao Jian

机构信息

Department of Pharmacy, Affiliated Cixi People's Hospital, Wenzhou Medical University, Ningbo, Zhejiang, 315300, China.

Institute of Molecular Pharmacology, School of Pharmaceutics Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.

出版信息

Oncotarget. 2017 Oct 27;8(60):102067-102077. doi: 10.18632/oncotarget.22155. eCollection 2017 Nov 24.

Abstract

Cerebrovascular disease such as stroke is one of the most common diseases in the aging population, and neural stem cells (NSCs) transplantation may provide an alternative therapy for cerebral ischemia. However, a hostile microenvironment in the ischemic brain offers is challenging for the survival of the transplanted cells. Considering the neuroprotective role of basic fibroblast growth factor (bFGF), the present study investigated whether bFGF gene-modified NSCs could improve the neurological function deficit after transient middle cerebral artery occlusion (MCAO) in adult male Sprague-Dawley rats. These rats were intravenously injected with modified NSCs (5×10/200 μL) or vehicle 24 h after MCAO. Histological analysis was performed on days 7 and 28 after tMCAO. The survival, migration, proliferation, and differentiation of the transplanted modified C17.2 cells in the brain were improved. In addition, the intravenous infusion of NSCs and gene-modified C17.2 cells improved the functional recovery as compared to the control. Furthermore, bFGF promoted the C17.2 cell growth, survival, and differentiation into mature neurons within the infarct region. These data suggested that bFGF gene-modified NSCs have the potential to be a therapeutic agent in brain ischemia.

摘要

诸如中风之类的脑血管疾病是老年人群中最常见的疾病之一,而神经干细胞(NSCs)移植可能为脑缺血提供一种替代疗法。然而,缺血性脑内的恶劣微环境对移植细胞的存活构成挑战。考虑到碱性成纤维细胞生长因子(bFGF)的神经保护作用,本研究调查了bFGF基因修饰的神经干细胞是否能改善成年雄性Sprague-Dawley大鼠短暂性大脑中动脉闭塞(MCAO)后的神经功能缺损。这些大鼠在MCAO后24小时静脉注射修饰的神经干细胞(5×10/200μL)或赋形剂。在tMCAO后第7天和第28天进行组织学分析。脑内移植的修饰C17.2细胞的存活、迁移、增殖和分化得到改善。此外,与对照组相比,静脉输注神经干细胞和基因修饰的C17.2细胞改善了功能恢复。此外,bFGF促进了C17.2细胞在梗死区域内的生长、存活并分化为成熟神经元。这些数据表明,bFGF基因修饰的神经干细胞有潜力成为脑缺血的治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be83/5731935/37d7350dd6cf/oncotarget-08-102067-g001.jpg

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