Mesenchymal stem cells (MSCs) have been induced to differentiate successfully from human embryonic stem cells (hES-MSCs), which could serve as an in vitro source of MSCs However, the homing behaviors of such cells and their potential utility for liver regeneration in vivo have not been reported We investigated factors that influenced early homing and the hepatic-directed differentiation potency of hES-MSCs in a mouse model of acute liver injury The hES-MSCs could be detected 36 h after cell infusion and this was unaffected by the number of cell passages in culture Pretreatment of hES-MSCs with TNF-alpha resulted in higher rates of homing of these cells to the injured liver Interestingly most of the cells homing at an early stage expressed alpha-fetoprotein (AFP), indicating hepatic differentiation Thus, hES-MSCs can home to the acutely injured liver at high efficiency and undergo hepatic differentiation, suggesting that these cells could be useful for treating acute human liver injury (C) 2010 Elsevier Inc All rights reserved