Mesenchymal stem cell–conditioned medium reduces liver injury and enhances regeneration in reduced-size rat liver transplantation

Abstract

BackgroundMesenchymal stem cell (MSC) therapy can prevent parenchymal cell loss and promotes tissue repair through the action of trophic, secreted molecules. In this study, we investigated whether MSC-conditioned medium (MSC-CM) could protect hepatocytes and sinusoidal endothelial cells (SECs) and stimulate their regeneration in 50% reduced-size liver transplantation (RSLT). Materials and methodsRats were randomly divided into three groups: sham-operated group, MSC-CM group (rats with 50% RSLT receiving MSC-CM infusion), and medium group (rats with 50% RSLT receiving medium therapy). Graft function, proinflammatory cytokines, incidence of apoptosis, proliferation of hepatocytes and SECs, and the expression of vascular endothelial growth factor and matrix metallopeptidase 9 were assessed in this study. ResultsSystemic infusion of MSC-CM prevented the release of liver injury biomarkers and provided a significant survival benefit. Furthermore, MSC-CM therapy resulted in reduction of apoptosis of hepatocytes and SECs. The number of proliferating hepatocytes and SECs increased 1.2- and 1.6-fold, respectively, accompanied by a decrease in the expression levels of several proinflammatory cytokines and a noticeable decrease in infiltration of neutrophils and activation of Kupffer cells. Also, increased expression of vascular endothelial growth factor and matrix metallopeptidase 9 in the grafts was observed after MSC-CM therapy. ConclusionsThese data suggest that MSC-CM therapy in RSLT provides trophic support to the injured liver by inhibiting SEC and hepatocellular death and stimulating their regeneration.