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Umbilical Cord Mesenchymal Stem Cells Conditioned Medium Promotes Aβ25-35 phagocytosis by Modulating Autophagy and Aβ-Degrading Enzymes in BV2 Cells

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Abstract

Mesenchymal stem cell (MSC) therapy is a promising prospect for the treatment of Alzheimer’s disease (AD); however, the underlying mechanisms by which MSCs mediate positive effects are still unclear. We speculated that MSCs mediate microglial autophagy and enhance the clearance of Aβ. To test this hypothesis, we cultured BV2 microglial cells with umbilical cord mesenchymal stem cells conditioned medium (ucMSCs-CM) in the presence or absence of Aβ25–35 oligomers. We investigated BV2 cell proliferation, cell death, and Aβ25–35 phagocytosis as well as protein expression levels of LC3, Beclin-1, p62, insulin-degrading enzyme (IDE), and neprilysin (Nep) with western blotting. The results showed that ucMSCs-CM inhibited the proliferation and decreased cell death of BV2 cells induced by Aβ25–35. ucMSCs-CM also promoted the phagocytosis of Aβ25–35 by BV2 cells and changed the expression of autophagy-related proteins LC3, Beclin-1, and p62. Treatment also upregulated the expression of Aβ-degrading enzymes IDE and Nep. Furthermore, the culture medium in BV2 cells with Aβ25–35 and ucMSCs-CM prevented neuronal cell SH-SY5Y from cell death compared to control medium without ucMSCs-CM. Altogether, these data suggested that ucMSCs-CM protect microglial and neuronal cells from Aβ25–35-induced cell death and promote Aβ phagocytosis by modulating autophagy and enhancing the expression of Aβ-degrading enzymes in microglia.

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Acknowledgements

We would like to thank Editage [www.editage.cn] for English language editing. This study was supported by the Doctoral Research Start-up Fund of Xinxiang Medical University, Scientific Research Fund of Xinxiang Medical University (2013QN122), Postdoctoral Research Fund of Henan Province (2013041), Project of Science and Technology Department of Henan Province (162102310493), Key Project of Science and Technology Research of Henan Provincial Education Department (14B180027), National Natural Science Foundation of China (131600791, 81771226), Xinxiang City Foundation (CXRC16003 and ZD17008), Xinxiang Medical University Foundation (20172DCG-03), and National Training Program of Innovation and Entrepreneurship for Undergraduates of China (201610472051).

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  1. Zhihao Xu and Wenbin Nan contributed equally to this work.

Authors and Affiliations

  1. Stem Cells and Biotherapy Engineering Research Center of Henan, School of Life Science and Technology, Xinxiang Medical University, East of JinSui Road, Xinxiang City, 453003, Henan Province, China

    Zhihao Xu, Wenbin Nan, Xiaoyue Zhang, Yuliang Sun, Jichao Yang, Kecheng Lu, Yalin Liu, Yaoxin Gao, Fen Yang, Xuekun Xing, Han Li, Yonghai Li, Huigen Feng, Zhiqing Yuan & Juntang Lin

  2. Postdoctoral Research Station of Biology, Henan Normal University, Xinxiang, China

    Zhihao Xu

  3. College of Biomedical Engineering, Xinxiang Medical University, East of JinSui Road, Xinxiang City, 453003, Henan Province, China

    Fen Yang, Jiang Du & Juntang Lin

  4. Hualong Biological Technology Co. Ltd., Xinxiang, China

    Wenchao Mao

  5. Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China

    Han Li & Juntang Lin

  6. Advanced Medical and Dental Institute, Universiti Sains Malaysia, 11 Bertam, Penang, Malaysia

    Han Li

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  1. Zhihao Xu
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Xu, Z., Nan, W., Zhang, X. et al. Umbilical Cord Mesenchymal Stem Cells Conditioned Medium Promotes Aβ25-35 phagocytosis by Modulating Autophagy and Aβ-Degrading Enzymes in BV2 Cells. J Mol Neurosci 65, 222–233 (2018). https://doi.org/10.1007/s12031-018-1075-5

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