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Journal of Molecular Neuroscience

, Volume 65, Issue 2, pp 222–233 | Cite as

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

  • Zhihao Xu
  • Wenbin Nan
  • Xiaoyue Zhang
  • Yuliang Sun
  • Jichao Yang
  • Kecheng Lu
  • Yalin Liu
  • Yaoxin Gao
  • Fen Yang
  • Wenchao Mao
  • Xuekun Xing
  • Jiang Du
  • Han Li
  • Yonghai Li
  • Huigen Feng
  • Zhiqing Yuan
  • Juntang Lin
Article

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.

Keywords

Mesenchymal stem cells Conditioned medium Microglia Aβ Autophagy 

Notes

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).

Compliance with Ethical Standards

Disclosure of Potential Conflicts of Interest

All authors have no conflict of interest to declare.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Zhihao Xu
    • 1
    • 2
  • Wenbin Nan
    • 1
  • Xiaoyue Zhang
    • 1
  • Yuliang Sun
    • 1
  • Jichao Yang
    • 1
  • Kecheng Lu
    • 1
  • Yalin Liu
    • 1
  • Yaoxin Gao
    • 1
  • Fen Yang
    • 1
    • 3
  • Wenchao Mao
    • 4
  • Xuekun Xing
    • 1
  • Jiang Du
    • 3
  • Han Li
    • 1
    • 5
    • 6
  • Yonghai Li
    • 1
  • Huigen Feng
    • 1
  • Zhiqing Yuan
    • 1
  • Juntang Lin
    • 1
    • 3
    • 5
  1. 1.Stem Cells and Biotherapy Engineering Research Center of Henan, School of Life Science and TechnologyXinxiang Medical UniversityXinxiang CityChina
  2. 2.Postdoctoral Research Station of BiologyHenan Normal UniversityXinxiangChina
  3. 3.College of Biomedical EngineeringXinxiang Medical UniversityXinxiang CityChina
  4. 4.Hualong Biological Technology Co. Ltd.XinxiangChina
  5. 5.Henan Key Laboratory of Medical Tissue RegenerationXinxiang Medical UniversityXinxiangChina
  6. 6.Advanced Medical and Dental InstituteUniversiti Sains MalaysiaPenangMalaysia

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