[Perisinusoidal stellate cells or Ito cells and their role in hepatic fibrosis]

In this review on stellate cells, discovered by Kupffer more than 100 years ago, morphological and ultrastructural aspects, origin and differentiation are described through also a comparative analysis in some animal species. Many methods used from different laboratories for isolation, identification and in vitro culture of these heterogeneous cells are reported and discussed regarding advantages and disadvantages. The normal Ito cells functions, that are metabolism and storage of vitamin A, extracellular matrix (ECM) synthesis under cytokines control, and sinusoidal tonus through its reversible contraction are discussed. Then an update description is reported about fibrogenesis and all the factors involved in liver fibrosis, from cytokines to the adhesion molecules. Stellate cells being the main source of ECM in chronic liver injury, can play different and primary roles by shifting its functions toward fibrosis. The role of metalloproteinases and their inhibitors on the balance of the ECM synthesis and degradation are also evaluated. When liver is injured, Ito cells became activated and change their phenotype from fat-storing cells to cells to cell devoid of retonoid droplets. They express the smooth muscle-like features, including a-SM-actin. The role of vitamin A in liver fibrosis is not yet clear: current data and hypothesis about this topic are discussed. Contractile behaviour of the perisinusoidal stellate cells seems also important in influencing portal blood pressure during fibrosis and cirrhosis. Diagnostic methods for hepatic fibrosis and Ito cells activation are also briefly reported. The review is supplied with more than three hundred references updated to August 1994.