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MicroRNA Let-7f-5p Promotes Bone Marrow Mesenchymal Stem Cells Survival by Targeting Caspase-3 in Alzheimer Disease Model

Linlin HanDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaYan ZhouDepartment of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaRuiyi ZhangDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaKaimin WuDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaYanhui LuDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaYanfei LiDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaRanran DuanDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaYaobing YaoDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDengna ZhuDepartment of Children Rehabilitation, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaYanjie JiaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

2018en

ABI

Annotatsiya

Widespread death of transplanted mesenchymal stem cells (MSCs) hampers the development of stem cell therapy for Alzheimer disease (AD). Cell pre-conditioning might help cope with this challenge. We tested whether let-7f-5p-modified MSCs could prolong the survival of MSCs after transplantation. When exposed to Aβ25-35 in vitro, MSCs showed significant early apoptosis with decrease in the let-7f-5p levels and increased caspase-3 expression. Upregulating microRNA let-7f-5p in MSCs alleviated Aβ25-35-induced apoptosis by decreasing the caspase-3 levels. After computerized analysis and the luciferase reporter assay, we identified that caspases-3 was the target gene of let-7f-5p. In vivo, hematoxylin and eosin staining confirmed the success of MSCs transplantation into the lateral ventricles, and the let-7f-5p upregulation group showed the lowest apoptotic rate of MSCs detected by TUNEL immunohistochemistry analysis and immunofluorescence. Similarly, bioluminescent imaging showed that let-7f-5p upregulation moderately prolonged the retention of MSCs in brain. In summary, we identified the anti-apoptotic role of let-7f-5p in Aβ25-35-induced cytotoxicity, as well as the protective effect of let-7f-5p on survival of grafted MSCs by targeting caspase-3 in AD models. These findings show a promising approach of microRNA-modified MSCs transplantation as a therapy for neurodegenerative diseases.

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Identifikatorlar

DOI: 10.3389/fnins.2018.00333

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