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

Guangfeng Chen, Yinpeng Jin, Xiujuan Shi, Yu Qiu, Yushan Zhang, Mingliang Cheng, Xiaojin Wang, Chengwei Chen, Yinxia Wu, Fuzhu Jiang, Li Li, Heng Zhou, Qingchun Fu, Xiaoqing Liu

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 approach. Hence, we investigate whether human adipose derived stem cell (ASC) has the therapeutic potential for ALF in this study based upon the studies of rat models. Sprague Dawley (SD) rats were used to establish ALF models by D-galactosamine (D-gal) injection. These rats were randomly divided into the human ASC treated group and the phosphate buffered saline (PBS) control group. The human ASCs or PBS were 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 femoral vain of rats to investigate the therapeutic potential for ALF. The ASC transplantation group showed improved viability than 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 three days. In addition, both concentrated serum-free ASC conditional media and ASC lysates, characterized by high levels of HGF and VEGF, demonstrated obvious improvement in terms of high survival rates of ALF rats. Our data suggest that ASC transplantation has the potential for acute liver failure treatment partly by the mechanism of secreting growth factors contributing to liver regeneration.