Published online Dec 7, 2017. doi: 10.3748/wjg.v23.i45.7978
Peer-review started: September 3, 2017
First decision: September 20, 2017
Revised: October 1, 2017
Accepted: November 1, 2017
Article in press: November 1, 2017
Published online: December 7, 2017
To investigate whether M1 or M2 polarization contributes to the therapeutic effects of mesenchymal stem cells (MSCs) in acute hepatic failure (AHF).
MSCs were transfused into rats with AHF induced by D-galactosamine (DGalN). 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 (EpCAM). 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.
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 EpCAM compared with the control groups (P < 0.001). Expression of EpCAM 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/mL vs 34.61 ± 6.6 pg/mL, 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/mL vs 104.07 ± 42.80 pg/mL, P < 0.001).
M2 polarization contributes to the therapeutic effects of MSCs in AHF by altering levels of anti-inflammatory and pro-inflammatory factors.
Core tip: M1 or M2 polarization governs the therapeutic effect of acute hepatic failure (AHF). Mesenchymal stem cells (MSCs) were transfused into rats with AHF induced by galactosamine. It was found that MSCs alleviated the survival rate and biochemical indicators by promoting hepatocyte regeneration. Immunohistochemistry, flow cytometry, and RT-PCR showed that M2 polarization contributes to the rescue of AHF by MSCs in the survival group after MSC transplantation. In addition, in the death group after MSC transplantation, the number of M1 macrophages increased significantly. Our findings suggest that M2 polarization contributes to the rescue of AHF by MSCs, which result in altered levels of anti-inflammatory and pro-inflammatory factors.