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

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.

RETRACTED: Resveratrol Preincubation Enhances the Therapeutic Efficacy of hUC-MSCs by Improving Cell Migration and Modulating Neuroinflammation Mediated by MAPK Signaling in a Mouse Model of Alzheimer’s Disease

“…To further explore the pathological change after hUC-MSCs transplantation, we studied neuro-inflammation in DG. A previous study demonstrated that the hUC-MSCs conditioned medium promoted the phagocytosis of Aβ25-35 by BV2 microglial cells in vitro and upregulated the expression of neprilysin and insulin-degrading enzymes, major proteases which cleave Aβ plaques (Xu et al, 2018). Aβ deposition is recognized as the main culprit for the pathological cascade of AD.…”

Attenuating Spinal Cord Injury by Conditioned Medium from Bone Marrow Mesenchymal Stem Cells

“…Interestingly, systemic MSCcm administration further increased LC3 II/I levels in the spinal cord. The autophagy-promoting effects by MSC graft [48], MSCcm [49] or MSC exosomes [50,51] have been reported in culture or in vivo studies, although not have not been seen in an SCI rat model. Additional experiments are warranted to determine the relation and role of individual RNA, miRNA and related protein elements of exosomes and SCI autophagy.…”

Graphene oxide enhances β-amyloid clearance by inducing autophagy of microglia and neurons

“…Since an increase in the autophagy capacity of microglial cells could induce the microglia to phagocytose [43], the ability of microglia to phagocytize Aβ was tested.…”