Mesenchymal stem cells rescue acute hepatic failure by polarizing M2 macrophages

AIM To investigate whether M1 or M2 polarization contributes to the therapeutic effects of mesenchymal stem cells(MSCs) in acute hepatic failure(AHF).METHODS MSCs were transfused into rats with AHF induced by D-galactosamine(DGal N). The therapeutic effects of MSCs were evaluated based on survival r...

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Published in:World journal of gastroenterology : WJG 2017-12, Vol.23 (45), p.7978-7988
Main Authors: Li, Yan-Wei, Zhang, Chong, Sheng, Qiu-Ju, Bai, Han, Ding, Yang, Dou, Xiao-Guang
Format: Article
Language:English
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Basic Study
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Summary:AIM To investigate whether M1 or M2 polarization contributes to the therapeutic effects of mesenchymal stem cells(MSCs) in acute hepatic failure(AHF).METHODS MSCs were transfused into rats with AHF induced by D-galactosamine(DGal N). The therapeutic effects of MSCs were evaluated based on survival rate and hepatocyte proliferation and apoptosis. Hepatocyte regeneration capacity was evaluated by the expression of the hepatic progenitor surface marker epithelial cell adhesion molecule(Ep CAM). Macrophage polarization was analyzed by M1 markers [CD68,tumor necrosis factor alpha(TNF-α),interferon-γ(IFN-γ),inducible nitric oxide synthase(INOS)] and M2 markers [CD163,interleukin(IL)-4,IL-10,arginase-1(Arg-1)] in the survival and death groups after MSC transplantation.RESULTS The survival rate in the MSC-treated group was increased compared with the DPBS-treated control group(37.5% vs 10%). MSC treatment protected rats with AHF by reducing apoptotic hepatocytes and promoting hepatocyte regeneration. Immunohistochemical analysis showed that MSC treatment significantly increased the expression of Ep CAM compared with the control groups(P < 0.001). Expression of Ep CAM in the survival group was significantly up-regulated compared with the death group after MSC transplantation(P = 0.003). Transplantation of MSCs significantly improved the expression of CD163 and increased the gene expression of IL-10 and Arg-1 in the survival group. IL-4 concentrations were significantly increased compared to the death group after MSC transplantation(88.51 ± 24.51 pg/m L vs 34.61 ± 6.6 pg/m L,P < 0.001). In contrast,macrophages showed strong expression of CD68,TNF-α,and INOS in the death group. The concentration of IFN-γ was significantly increased compared to the survival group after MSC transplantation(542.11 ± 51.59 pg/m L vs 104.07 ± 42.80 pg/m L,P < 0.001).CONCLUSION M2 polarization contributes to the therapeutic effects of MSCs in AHF by altering levels of anti-inflammatory and pro-inflammatory factors.
ISSN:1007-9327
2219-2840
DOI:10.3748/wjg.v23.i45.7978