Recent studies have demonstrated that conditioned media derived from mesenchymal stem cells (MSCs-CM) have therapeutic effects in various experimental diseases. However, the therapeutic mechanism is not fully understood. Here we investigated the therapeutic effects and mechanism of MSCs-CM in experimental anti-glomerular basement membrane (GBM) glomerulonephritis (GN). We administered either MSCs-CM or vehicle from day 0 up to day 10 following induction of nephrotoxic serum nephritis in Wistar-Kyoto rats. In vitro, we analyzed the effects of MSCs-CM on TNF-α-mediated cytokine production in cultured mesangial cells (NHMC), proximal tubular cells (HK-2), endothelial cells (HUVEC), and monocytes (THP-1 and PBMC). Compared to vehicle treatment, MSCs-CM treatment improved proteinuria and renal dysfunction. Histologically, MSCs-CM-treated rats had reduced crescent formation and glomerular ED1+ macrophage infiltration, and increased glomerular ED2+ macrophage infiltration. Increased serum MCP-1 levels were observed in MSCs-CM-treated rats. Renal cortical mRNA expression levels of pro-inflammatory cytokines, such as TNF-α and IL-6 and of the Th1 cytokine IFN-γ were greatly decreased by MSCs-CM treatment. In vitro, pretreatment with MSCs-CM blocked TNF-α-mediated IL-8 release in NHMC and HK-2 cells. TNF-α-mediated MCP-1 release was enhanced by pretreatment with MSCs-CM in HUVEC and HK-2 cells, and was strikingly enhanced in THP-1 cells. Stimulation of PBMC with a combination of MCP-1 and IL-4 enhanced the expression of M2-associated genes compared to IL-4 alone. We demonstrated that MSCs-CM had therapeutic effects in experimental anti-GBM GN that were mediated through anti-inflammatory effects that were partly due to acceleration of M2 macrophage polarization, which might be mediated by MCP-1 enhancement.
- conditioned media
- stem cells
- Copyright © 2016, American Journal of Physiology - Renal Physiology