Transplantation of Hepatocytelike Cells Derived from Umbilical Cord Stromal Mesenchymal Stem Cells to Treat Acute Liver Failure Rat

Abstract

Background: Liver transplantation is the ultimate treatment for liver failure. However, its use is complicated by shortage of donor organs and numerous other problems. Thus, other methods for the treatment of liver failure, including cell therapy, are being considered. We have evaluated the capacity of hepatocyte-like cells differentiated from Wharton’s jelly mesenchymal stem cells (WJ-MSCs) to prevent or ameliorate acute liver failure in a rat model. Methods: WJ-MSCs were isolated from human umbilical cords and induced to differentiate into hepatocyte-like cells by incubation with a combination of liver-tissue culture medium and growth factors. The differentiated cells were evaluated with immunocytochemistry, RT-PCR, ammonia metabolism test, and glycogen storage for characteristics of functioning hepatocytes. The hepatocyte-like cells were transplanted into the portal vein of rats with acute liver failure induced by carbontetrachloride injection. Survival, serum liver function tests, and body weight of the animals were recorded. Livers of the rats 30 days after transplantation were harvested. Results: The differentiated hepatocyte-like cells had morphologic features and functional characteristics of mature hepatocytes: hepatocyte-related genes, conversion of ammonia to urea, albumin synthesis, glycogen storage, and declining values of alpha-fetoprotein. Transplantation of the hepatocyte-like cells into the rats with carbon tetrachloride-induced liver failure prevented death of the animals and prevented rising values of serum alanine transaminase (ALT), aspartate transaminase (AST), and bilirubin. Immunohistochemical study of rat liver tissues 30 days after transplantation revealed that the WJ-MSCs had survived and were producing albumin. Conclusions: WJ-MSCs of the human umbilical cord were could differentiated into hepatocyte-like cells in vitro. Transplantation of hepatocyte-like cells into the portal vein of rats with carbontetrachloride acute liver injury prevented death of the animals and irreversible liver injury. These findings may serve as a reference for future research in cell therapy of liver failure.