Adipose-derived stem cell-based treatment for acute liver failure

Abstract

Introduction: Acute liver failure (ALF) is a highly lethal disease, for which effective therapeutic methods are limited. Although allogeneic liver transplantation is a viable treatment method for ALF, there is a serious shortage of liver donors. Recent studies suggest that stem cell transplantation is a more promising alternative. Hence, we investigate whether human adipose-derived stem cells (ASCs) have the therapeutic potential for ALF in this study based on the studies of rat models. Methods: Sprague Dawley rats were used to establish ALF models by D-galactosamine injection. These rats were randomly divided into a human ASC-treated group and a phosphate-buffered saline (PBS) control group. The human ASCs or PBS was transplanted through the spleen of rats. The indices of hepatic function and hepatic histology were dynamically detected, and the survival rates of rats were also counted. Double-fluorescence immunohistochemistry was employed to detect the ASC fate after transplantation. Moreover, both concentrated ASC conditional media and ASC lysates were transplanted through the femoral vain of rats to investigate the therapeutic potential for ALF. Results: The ASC transplantation group showed improved viability in comparison with the sham control. Histological and biochemical analysis suggested that liver morphology and function were improved in terms of cell proliferation and apoptosis. Although a plethora of ASCs persist in the spleen, the improvement in liver function was obvious. However, ASCs did not differentiate into hepatocytes after engrafting to livers within 3 days. In addition, both concentrated serum-free ASC conditional media and ASC lysates, characterized by high levels of hepatocyte growth factor and vascular endothelial growth factor, demonstrated obvious improvement in terms of high survival rates of ALF rats. Conclusion: Our data suggest that ASC transplantation has the potential for ALF treatment partly by the mechanism of secreting growth factors contributing to liver regeneration.