No abstract

Therapeutic Study, Level IV (case series). See the Guidelines for Authors for a complete description of levels of evidence.

Adult hepatic progenitor cells are activated during regeneration when hepatocytes and bile duct epithelium are damaged or unable to proliferate. On the basis of its role as a tumor suppressor and in the potential malignant transformation of stem cells in hepatocellular carcinoma, we investigated the role of key transforming growth factor beta (TGF-␤) signaling components, including the Smad3 adaptor protein ␤2-Spectrin (␤2SP), in liver regeneration. We demonstrate a streaming hepatocyte-specific dedifferentiation process in regenerating adult human liver less than 6 weeks following living donor transplantation. We then demonstrate a spatial and temporal expansion of TGF-␤ signaling components, especially L iver regeneration involves a complex sequence of signaling events to restore liver mass and function. Following two-thirds partial hepatectomy, 95% of differentiated hepatocytes exit G 0 and synchronously reenter the cell cycle. DNA synthesis begins within 24 hours and peaks 36-48 hours posthepatectomy in most mouse strains. 1 Restoration of liver mass is nearly complete by 5-7 days in rodents and by 3-4 months in humans. 2 When hepatocytes and bile duct epithelium are severely damaged or unable to proliferate, a population of hepatic progenitor cells is activated. These progenitors represent a heterogeneous spectrum of cells that express markers corresponding to both the hepatocytic and cholangiocytic lineages and serve as a source of cell replenishment and tissue repair as they differentiate into either cell type, thereby aiding in liver regeneration. 3,4 Hepatic progenitor cells have been described to reside and originate from several potential sources including the canals of Hering, intralobular bile ducts, periductal mononuclear cells, and peribiliary hepatocytes. 5 To date, progenitor