Fig. 8: Schematic of how BM-MSCs may decrease liver fibrosis by targeting Ly6Chi/lo macrophages through activating the cytokine-paracrine and apoptotic pathways.

CCL2 secreted by the fibrotic liver promoted the recruitment of Ly6Chi monocytes from bone marrow to the liver. BM-MSC transplantation promoted the conversion of Ly6Chi to Ly6Clo macrophages by secreting cytokines IL4 and IL10, which decreased the activation of HSCs. Meanwhile, BM-MSCs experienced severe apoptosis and produced substantial apoptotic bodies, which were engulfed by Ly6Clo macrophages, leading to MMP12 release and accelerated extracellular matrix (ECM) degradation in CCL4-induced liver fibrosis.