Pathogenic and therapeutic roles of mesenchymal stem cells in liver fibrosis

The aim of this study was to conduct a comparative analysis of the bioregulatory role of mesenchymal stem cells (MSCs) in the liver under physiological conditions, in acute and chronic injury with fibrotic remodeling, and during therapeutic correction by implanting exogenous MSCs from healthy tissues into the body. The analysis showed that hepatic MSCs maintain structural homeostasis by interacting with tissue myofibroblasts and migrating immune cells. In acute liver injury that does not deplete adaptive reserves, hepatic (resident) MSCs regulate tissue homeostasis.. Chronic injury that depletes adaptive reserves activates both immune cells and hepatic MSCs, leading to liver inflammation and the transdifferentiation of MSCs into myofibroblasts. These activated fibroblasts overproduce extracellular matrix components, thereby driving liver fibrosis progression. Exogenous apoptotic MSCs from healthy auto- or allogeneic tissues, when administered in cases of chronic liver injury, can compensate for deficient regulatory factors and restore metabolic regulation and structural homeostasis through their paracrine and trophic activity. Their therapeutic potential is maximized when their regulatory properties are enhanced prior to administration and when applied in recipients without irreversible liver injury.