Electron microscopic identification of putative liver stem cells and intermediate hepatocytes following periportal necrosis induced in rats by allyl alcohol.

The ultrastructural characteristics of the putative liver stem cells that repopulate the necrotic periportal zones after allyl alcohol induced liver injury are described. Periportal liver cell necrosis was induced in adult female Sprague-Dawley rats by i.p. injection with 0.62 mmol/kg of allyl alcohol. Electron microscopic examination of the livers was carried out at 33, 57, 81 and 129 h after injection. After periportal necrosis small nondescript intraportal cells (putative liver stem cells) as well as three type of "progenitor" cells are seen: type I, immature "precursor" cells; type II, bile duct-like; and type III, hepatocyte-like, with numerous cells of intermediate type between type I and type III. The periportal necrotic zone (zone I) is reconstituted largely by an increase in hepatocyte-like cells containing mitochondria, lysosomes, lipid-filled vacuoles, rare peroxisomes, prominent endoplasmic reticulum and lateral microvilli (type III cells) with a relatively small number of type I (immature) cells participating. The type III cells display different degrees of differentiation; the less mature are termed "restitutive" and the more mature "transitional" hepatocytes to emphasize the probable relationship between these cell types. Immature ductular cells (type II cells) are seen located basally within hyperplastic ducts in the periportal zone. It is postulated that hepatocyte restitution after periportal necrosis is accomplished by proliferation and differentiation of stem cells with both biliary and hepatic potential that specifically differentiate into hepatic cells through "restitutive" and "transitional" intermediates. These postulated liver stem cells may be intraportal cells seen 33-57 h after injury that precede the type I and type III hepatic precursors seen later.