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Effect of growth differentiation factor-15 secreted by human umbilical cord blood-derived mesenchymal stem cells on amyloid beta levels in in vitro and invivo models of Alzheimer's disease.

Authors: Kim, Dong Hyun  Lee, Dahm  Lim, Hoon  Choi, Soo Jin  Oh, Wonil  Yang, Yoon Sun  Chang, Jeong Ho  Jeon, Hong Bae 
Citation: Kim DH, etal., Biochem Biophys Res Commun. 2018 Sep 14. pii: S0006-291X(18)31922-3. doi: 10.1016/j.bbrc.2018.09.012.
Pubmed: (View Article at PubMed) PMID:30224067
DOI: Full-text: DOI:10.1016/j.bbrc.2018.09.012

Alzheimer's disease (AD), which is the most common progressive neurodegenerative disease, causes learning and memory impairment. The pathological progress of AD can derive from imbalanced homeostasis of amyloid beta (Aß) in the brain. In such cases, microglia play important roles in regulating the brain Aß levels. In the present study, we found that human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) can increase, through paracrine action, the ability of microglial cells to clear Aß. In order to identify the associated paracrine factors, a secretome of hUCB-MSCs co-cultured with Aß-treated BV2 microglial cells was analyzed using a human cytokine protein array. As a result, growth differentiation factor-15 (GDF-15) was identified as a predominant candidate, and its association with Aß clearance by microglial cells was investigated in vitro and in a 5XFAD mouse model. When Aß-treated BV2 cells were treated with exogenous recombinant GDF-15, the Aß levels in the culture medium decreased. Moreover, GDF-15 injection in the brain parenchyma of 5XFAD mice also led to decrease in Aß plaques. In contrast, co-culture of BV2 cells and hUCB-MSCs treated with GDF-15-specific siRNA did not influence the Aß levels in the culture medium. To elucidate how these phenomena are related, we confirmed that GDF-15 specifically increases insulin-degrading enzyme (IDE) expression in microglial cells through TGFß receptor type II (TGFßRII), both in vitro and in vivo. These findings suggest that hUCB-MSCs promote the Aß clearance ability of microglial cells through regulation of GDF-15 secretion, thus elucidating a therapeutic mechanism for AD.


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RGD Object Information
RGD ID: 13792790
Created: 2018-09-28
Species: All species
Last Modified: 2018-09-28
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.