Protective effects of mesenchymal stem cells overexpressing extracellular regulating kinase 1/2 against stroke in rats
| Autor: | Dandan Wu, Ling Dou, Yiiie Zhang, Huanhuan Li, Bin Ma, Xiaoqing Gao, Haibo Zhang, Qionglan Yuan, Jiaqi Zeng, Lifen Liu, Chao-Xian Yang, Liang Huang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Male MAP Kinase Signaling System Mesenchymal Stem Cell Transplantation Brain Ischemia 03 medical and health sciences 0302 clinical medicine Neural Stem Cells Medicine Animals Rats Wistar Neuroinflammation Cells Cultured Mitogen-Activated Protein Kinase 1 Neurons Mitogen-Activated Protein Kinase 3 Kinase business.industry General Neuroscience Mesenchymal stem cell Cell Differentiation Infarction Middle Cerebral Artery Mesenchymal Stem Cells Recovery of Function Nestin Neural stem cell Rats Transplantation Stroke Disease Models Animal 030104 developmental biology Cancer research Tumor necrosis factor alpha business 030217 neurology & neurosurgery |
| Zdroj: | Brain research bulletin. 149 |
| ISSN: | 1873-2747 |
| Popis: | Objective Although transplantation of bone marrow-derived mesenchymal stem cells (MSCs) has shown beneficial effects on stroke, lower survival of MSCs limits effects. Extracellular regulating kinase 1/2 signaling (ERK1/2) is crucial for cell survival, differentiation, and proliferation. This study was designed to explore whether MSCs modified by over-expressing ERK1/2 may reinforce beneficial effects on stroke in rats. Methods rat MSCs transfected with ERK1/2 and empty lentivirus to generate MSCs overexpressing ERK1/2 (ERK/MSCs) and MSCs (as a control), respectively. In vitro, ERK/MSCs were plated and exposed to glutamate-induced condition, and viability of ERK/MSCs was measured. Furthermore, neural induction of ERK/MSCs was investigated in vitro. Cerebral ischemic rats were induced by occluding middle cerebral artery, and then were stereotaxically injected into ipsilateral right lateral ventricle with ERK/MSCs or MSCs 3 days after stroke and survived for 7 or 14 days after injection. Results ERK/MSCs showed better viability in physiological and glutamate-induced neurotoxic conditions compared to MSCs. After neural induction, more neurons were be differentiated from ERK/MSCs than from MSCs. After transplantation, more numbers of grafted cells and improved functional recovery were observed in ERK/MSCs-treated rats compared with MSCs-treated rats. Compared with MSCs treatment, ERK/MSCs treatment significantly increased proliferation of neural stem cells in the subventricle zone (SVZ) and the MAP2/nestin double-labeled cells adjacent to the SVZ, enhanced the numbers of reactive astrocytes while suppressed microglial activation. Besides, TNF-α level was elevated in ERK/MSCs-treated rats. Conclusion:ERK/MSCs transplantation showed better functional recovery after stroke in rats, likely in part through enhancing survival of MSCs and possibly by modulating the proliferation, neuronal de-differentiation and neuroinflammation. |
| Databáze: | OpenAIRE |
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