Distribution of hepatic stem cell markers in human liver with massive hepatic necrosis

Background and aims: The origin, niche, and function of human hepatic stem/progenitor cells (HHSPCs) have been longstanding areas of debate. We designed this study to elucidate the distribution of potential HHSPCs during the various stages of regeneration by the expression of known HHSPC markers. Methods: Immunostainings for c-kit, cytokeratin (CK)19, and CD133 were performed in cases of massive hepatic necrosis (MHN) in various regenerating stages. Results: We identified c-kit-positive cells as single cells primarily in the stroma of portal tracts but rarely in the sinusoids. There were no differences in the numbers or distribution of c-kit positive cells according to MHN regeneration stage. The number of CK19-positive cells mostly in a ductular arrangement significantly increased along the interface, and single cells or small clusters of CK19-positive cells were occasionally observed in the sinusoid in cases of MHN. CD133-positive cells were located in ductular structures along the interface in cases of MHN, while no CD133-positive cells were observed in the normal liver. Conclusion: The c-kit- or CD133-positive cells appear first at the limiting plate and are then organized into ductular structures or moved to the sinusoid as single cells or clusters during hepatic regeneration.