Localization of liver myofibroblasts and hepatic stellate cells in normal and diseased rat livers: distinct roles of (myo-)fibroblast subpopulations in hepatic tissue repair

Previous in vitro studies indicated that hepatic stellate cells (HSC) and r at liver myofibroblasts (rMF) have to be regarded as different cell populat ions of the myofibroblastic lineage with fibrogenic potential. Employing th e discrimination features defined by these studies the localization of HSC and rMF was analyzed in diseased livers. Normal and acutely as well as chro nically carbon tetrachloride-injured livers were analyzed by immunohistoche mistry and by in situ hybridization. In normal livers HSC [desmin/glial fib rillary acid protein (GFAP)-positive cells] were distributed in the hepatic parenchyma, while rMF (desmin/smooth muscle alpha actin-positive, GFAP-neg ative cells colocalized with fibulin-2) were located in the portal field, t he walls of central veins, and only occasionally in the parenchyma. Acute l iver injury was characterized almost exclusively by an increase in the numb er of HSC, while the amount of rMF was nearly unchanged. In early stages of fibrosis, HSC and rMF were detected within the developing scars. In advanc ed stages of fibrosis, HSC were mainly present at the scar-parenchymal inte rface, while rMF accounted for the majority of the cells located within the scar. At every stage of fibrogenesis, rMF, in contrast to HSC, were only o ccasionally detected in the hepatic parenchyma. HSC and rMF are present in normal and diseased livers in distinct compartments and respond differentia lly to tissue injury. Acute liver injury is followed by an almost exclusive increase in the number of HSC, while in chronically injured livers not onl y HSC but also rMF are involved in scar formation.