Therapeutic potential of mesenchymal stem cells in the treatment of acute liver failure.

Abstract

Acute liver failure (ALF) is a severe and life-threatening condition in which rapid deterioration of liver function develops in a patient who has no preexisting liver disease. Mesenchymal stem cells (MSCs) are immunoregulatory stem cells which are able to modulate phenotype and function of all immune cells that play pathogenic role in the development and progression of ALF. MSCs in juxtacrine and paracrine manner attenuate antigen-presenting properties of dendritic cells and macrophages, reduce production of inflammatory cytokines in T lymphocytes, suppress hepatotoxicity of natural killer T (NKT) cells and promote generation and expansion of immunosuppressive T, B and NKT regulatory cells in acutely inflamed liver. Due to their nano-sized dimension and lipid envelope, intravenously injected MSC-derived exosomes (MSC-Exos) may by-pass all biological barriers to deliver MSC-sourced immunoregulatoy factors directly into the liver-infiltrated immune cells and injured hepatocytes. Results obtained by us and others revealed that intravenous administration of MSCs and MSC-Exos efficiently attenuated detrimental immune response and acute inflammation in the liver, suggesting that MSCs and MSC-Exos could be considered as potentially new remedies in the immunotherapy of ALF. In this review, we emphasize the current knowledge about molecular and cellular mechanisms which are responsible for MSC-based modulation of liver-infiltrated immune cells and we discuss different insights regarding the therapeutic potential of MSCs in liver regeneration.