Abstract
Human liver stem cell compartments are comprised of hepatic stem cells (HSCs), hepatoblasts (HBs), unipotent hepatic progenitors, and mesenchymal progenitors (angioblasts and stellate cell precursors), located in limiting plates in fetal livers and Canals of Hering in postnatal livers. The antigenic profiles and ex vivo clonogenic expansion conditions for each subpopulation have been defined. HSCs are found at 0.1–0.7% of the cells in livers of all age donors, are 7–10 um in diameter, form morphologically uniform colonies, and express EpCAM and an array of hepatocytic, biliary and stem cell markers but no hemopoietic markers, mesenchymal cell markers, or alpha-fetoprotein (AFP). The HSCs give rise to HBs, that are larger (10–12 um), with overlapping antigenic and biochemical profiles to HSCs but differ in expression of ICAM1, P450-3A7, AFP, and yield cord-like colonies with canaliculi. The HBs dwindle in numbers with donor age remaining as cell aggregates tethered to the ends of Canals of Hering. Enrichment for hepatic progenitors is achieved by immunoselection for EpCAM+ cells. Self-replication at ~one division/day and with high telomerase levels is observed under specific culture conditions. EpCAM+ cells form liver tissue when transplanted into scid/NOD mice. Potential medical applications include the treatment of liver disease by cell therapies such as cell transplantation and/or bioartificial livers.
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