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

Background: Mesenchymal 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 methods: Rats 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. Results: Systemic 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. Conclusions: These 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. (c) 2013 Elsevier Inc. All rights reserved.