ELECTRON-MICROSCOPIC IDENTIFICATION OF PUTATIVE LIVER STEM-CELLS AND INTERMEDIATE HEPATOCYTES FOLLOWING PERIPORTAL NECROSIS INDUCED IN RATSBY ALLYL ALCOHOL

The ultrastructural characteristics of the putative liver stem cells t hat repopulate the necrotic periportal zones after allyl alcohol induc ed liver injury are described. Periportal liver cell necrosis was indu ced in adult female Sprague-Dawley rats by i.p. injection with 0.62 mm ol/kg of allyl alcohol. Electron microscopic examination of the livers was carried out at 33, 57, 81 and 129 h after injection. After peripo rtal necrosis small nondescript intraportal cells (putative liver stem cells) as well as three types 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 ty pe I and type III. The periportal necrotic zone (zone I) is reconstitu ted largely by an increase in hepatocyte-like cells containing mitocho ndria, lysosomes, lipid-filled vacuoles, rare peroxisomes, prominent e ndoplasmic reticulum and lateral microvilli (type III cells) with a re latively small number of type I (immature) cells participating. The ty pe III cells display different degrees of differentiation; the less ma ture are termed ''restitutive'' and the more mature ''transitional'' h epatocytes to emphasize the probable relationship between these cell t ypes. Immature ductular cells (type II cells) are seen located basally within hyperplastic ducts in the periportal zone. It is postulated th at 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 post ulated liver stem cells may be intraportal cells seen 33-57 h after in jury that precede the type I and type III hepatic precursors seen late r.