Regulatory effects of mesenchymal stromal cells on the development of liver fibrosis: Cellular and molecular mechanisms and prospects of clinical application
Liver fibrosis represents an actual medical problem. Its progression can lead to liver failure, portal hypertension and hepatocellular carcinoma. The mechanisms underlying development of fibrosis include excess extracellular matrix production by activated hepatic stellate cells, inhibition of fibrolysis, oxidative damage and apoptosis of hepatocytes, inflammation, and capillarization of sinusoidal endothelium. Development of the pathological process is caused by mutual influence of several cell populations through different signaling pathways. Currently, the effectiveness of affecting liver fibrogenesis using pharmacological agents, surgery or exposure to physical factors is poor. Great hopes in this regard are placed on cell therapy using mesenchymal stromal cells. Their hepatoprotective and regenerative potential is primarily due to the paracrine secretion of a wide range of regulatory molecules that contribute to the survival and proliferation of hepatocytes, prevent activation and stimulate apoptosis of hepatic stellate cells, have immunomodulatory, proangiogenic and fibrolytic effects. The complex effect of mesenchymal stromal cells on different cell populations involved in the development of liver fibrosis gives reason to consider these cells and their secretory products (in particular, extracellular vesicles) as a promising resource for clinical use.