COMPARISON OF LIVER PROGENITOR CELLS IN HUMAN ATYPICAL DUCTULAR REACTIONS WITH THOSE SEEN IN EXPERIMENTAL-MODELS OF LIVER-INJURY

The ultrastructural characteristics of liver progenitor cell types of human atypical ductular reactions seen in chronic cholestasis, in rege nerating human liver after submassive necrosis, in alcoholic liver dis ease, and in focal nodular hyperplasia are compared with liver progeni tor cell types seen during experimental cholangiocarcinogenesis in ham sters; during hepatocarcinogenesis in rats; and in response to peripor tal liver injury induced by allyl alcohol in rats. Three types of prog enitor cells have been identified in human atypical ductular reactions : type I: primitive, has an oval shape, marginal chromatin, few cellul ar organelles, rare tonofilaments, and forms desmosomal junctions with adjacent liver cells; type II: bile duct-like, is located within duct s, has few organelles, and forms lateral membrane interdigitations wit h other duct-like cells; and type III: hepatocyte-like, is located in hepatic cords, forms a bile canaliculus, has tight junctions with othe r hepatocyte-like cells, prominent mitochondria and rough endoplasmic reticulum, and some have lysosomes and a poorly developed Golgi appara tus. Each type is seen during cholangiocarcinogenesis in hamsters, but the most prominent cell type is type II, duct-like. A more primitive cell type (''type 0 cell''), as well as type I cells, are seen in the intraportal zone of the liver within 1 to 2 days after carcinogen expo sure or periportal injury in the rat, but both type II and type III ar e seen later as the progenitor cells expand into the liver lobule. Aft er allyl alcohol injury, type 0 cells precede the appearance of type I and type III cells, but most of the cells that span the periportal ne crotic zone are type III hepatocyte-like cells showing different degre es of hepatocytic differentiation, Some type II cells are also seen, b ut these are essentially limited to ducts. It is concluded that there is a primitive stem cell type in the liver (type 0) that may different iate directly into type I and then into type II, duct-like or or type III hepatocyte-like cells. The terms oval cell, transitional hepatocyt e, biliary hepatocyte, hepatocyte-like cell, atypical ductular cell, n eocholangiole, etc., are used to describe these cells. Although these terms are useful as general descriptive terms for liver precursor cell s at the light microscopic level, the cells included in these descript ive categories may be very different from one another biologically and ultrastructurally.