The Effects of Programmed Cell Death of Mesenchymal Stem Cells on the Development of Liver Fibrosis

Figure 1

Mechanism of MSCs in reducing liver fibrosis. MSCs could increase the expression levels of anti-inflammatory cytokines (interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α)) and reduce the expression levels of proinflammatory cytokines (IL-6, IL-1A, IL-17, monocyte chemoattractant protein-1 (MCP-1), granulocyte colony-stimulating factor (GCSF), interferon-gamma (IFN-γ), macrophage inflammatory protein-2A (MIP-2A), and granulocyte-macrophage colony-stimulating factor (GMCSF)), thereby reducing hepatocyte injury and inhibiting the activation of hepatic stellate cells. MSCs enhance the generation of anti-inflammatory phenotypes in macrophages (M2 macrophages), phagocytic debris, and increase the production of MMP to reduce the degree of liver fibrosis. MSC-EVs inhibit the production of TNF-α, IL-1β, and collagen-1α, and thus reduce hepatocyte apoptosis and inhibit liver fibrosis. The ability of MSCs to differentiate into hepatocyte-like cells can be improved by adding cytokines and growth factors, regulating the microenvironment, and modifying genes, which could relieve liver fibrosis.