Horizons in TransplantationExperimental transplantationTransplantation of Adipose-Derived Mesenchymal Stem Cells Efficiently Rescues Thioacetamide-Induced Acute Liver Failure in Mice

•The transplantation of adipose-derived mesenchymal stem cells (ADMSCs) is effective in treating thioacetamide-induced acute liver failure.•Intravenous transplantation was found to be more effective than intrasplenic transplantation in rescuing liver failure.•The transplanted ADMSCs could engraft in the injured livers and differentiate into hepatocyte-like cells.

BackgroundWe aimed to investigate the efficacy of adipose-derived mesenchymal stem cell (ADMSC) transplantation in acute liver failure caused by thioacetamide in mice as well as its underlying mechanism by comparing transplantation routes.MethodsADMSCs were isolated from inguinal fat pads of enhanced green fluorescent protein (EGFP) transgenic mice and analyzed regarding their surface markers and differentiation potential. Acute liver failure models were established by infusion of thioacetamide, and then we injected EGFP-ADMSCs or phosphate-buffered saline solution by intrasplenic or intravenous route. The restoration of biologic functions of the livers receiving transplantation was assessed by means of a variety of approaches, such as survival rates, live function parameters, histology, localization of EGFP-ADMSCs, and immunofluorescence analysis.ResultsADMSCs were positive for CD90 and CD44 and negative for CD34 and had adipogenic and osteogenic differentiation potential. And they prevented the release of liver injury biomarkers. Transplantation via tail vein provided a significant survival benefit, but no significant differences were observed in the intrasplenic pathway and between the 2 pathways in our animal experiments. Furthermore, the transplanted cells were well integrated into injured livers and produced albumin and cytokeratin-8.ConclusionsDirect transplantation of ADMSCs is an effective treatment for acute liver failure rather than intrasplenic transplantation. The transplanted ADMSCs exhibit the potential to differentiate into hepatocyte-like cells in the injured livers. Thus, ADCMSCs would be a potential option for treatment of acute liver failure.

Graphical abstractDownload high-res image (179KB)Download full-size image(A) The survival rate of four groups: transplantation group via tail vein was prolonged significantly compared with the control group (ρ<0.05).(B) The EGFP-positive cells were widely distributed in the hepatic lobules on Day 14 in the group of intrasplenic injection after cell transplantation. Bar = 50 μm.