The mechanisms of liver regeneration remain unclear. Graft genotyping from living donor liver transplantation revealed the involvement of extrahepatic cells in liver regeneration. The transplantation of bone marrow-derived multilineage differentiating stress enduring (Muse) cells after physical partial hepatectomy in mice showed that Muse cells accumulated adjacent to the physically damaged lesion and subsequently differentiated into hepatocytes, cholangiocytes, and sinusoidal epithelial cells, suggesting that Muse cells can be of a candidate of extrahepatic cells involved in the liver regeneration. Muse cells can be effectively isolated as stage-specific embryonic antigen-3- (SSEA-3) positive from human bone marrow-derived mesenchymal stem cells, and demonstrated pluripotency that can differentiate the endodermal, ectodermal, and mesodermal cells. In contrast to other stem cell resources, Muse cells do not require gene transfection for the acquisition of the pluripotency and do not form tumors in vivo. These characteristics minimize ethical concerns in human cellular transplantation. Together with the characteristics of Muse cells, our results suggest that Muse cells may aid in liver tissue repair and regeneration after physical partial hepatectomy in humans.
