Therapeutic potential and related signal pathway of adipose‐derived stem cell transplantation for rat liver injury

Abstract

Liver transplantation is the only currently effective therapy for end-stage chronic liver disease and severe acute liver failure, but its use is limited by high cost and a shortage of allografts. Here we explored the effectiveness of transplanting adipose-derived stem cells (ADSCs) into rats with experimentally induced liver injury. ADSCs obtained from rats were hepatogenic induced in vitro with MAPK pathways inhibitors preconditioning. In vivo, ADSCs were transplanted into rats via different routes and serum liver function markers from post-operative rats were tested. When grown in adipogenic induction medium, ADSCs were able to differentiate into adipocytes. In hepatogenic induction medium, ADSCs were able to differentiate into hepatocyte-like cells, with appropriate changes in morphology and appropriately elevated expression of hepatocyte-specific markers. ERK1/2 phosphorylation activity was also significantly upregulated during the hepatogenic differentiation process, and was blocked by the ERK/MAPK pathway-specific inhibitor PD98059. In a rat liver injury model, intravenously injected ADSCs successfully engrafted into recipient livers. We found that injection via the hepatic portal vein was more efficient than via the dorsal vein of the penis. ADSC transplantation into damaged livers significantly decreased the level of serum liver enzymes such as alanine aminotransferase and aspartate aminotransferase, and improved serum albumin level. Both the number of engrafted cells and the improvement of liver function reached a peak two weeks after transplantation. Transplanted ADSCs appear to be therapeutically effective in the rat liver injury model, which may ultimately provide a therapeutic alternative to liver transplantation in human patients.