IDENTIFICATION, CULTURE, AND CHARACTERIZATION OF PANCREATIC STELLATE CELLS IN RATS AND HUMANS

Background & Aims: Until now, the basic matrix-producing cell type res ponsible for pancreas fibrosis has not been identified. In this report , retinoid-containing pancreatic stellate cells (PSCs) in rat and huma n pancreas are described, and morphological and biochemical similariti es to hepatic stellate cells are shown. Methods: Electron and immunofl uorescence microscopy (collagen types I and III, fibronectin, laminin, alpha-actin, and desmin) was performed using pancreatic tissue and cu ltured PSCs. Extracellular matrix synthesis was shown using quantitati ve immunoassay and Northern blot analysis. Results: PSCs are located i n interlobular areas and in interacinar regions. Early primary culture d PSCs contain retinol and fatty acid retinyl-esters. Addition of reti nol to passaged cells resulted in retinol uptake and esterification. D uring primary culture, the cells changed from a quiescent fat-storing phenotype to a highly synthetic myofibroblast-like cell expressing iso -alpha-smooth muscle actin (> 90%) and desmin (20%-40%) and showing st rong positive staining with antibodies to collagen types I and Iii, fi bronectin, and laminin. As determined on protein and messenger RNA lev el, serum growth factors stimulated the synthesis of collagen type I a nd fibronectin. Conclusions: The identification of PSCs, particularly in fibrotic areas, and the similarities of these cells to hepatic stel late cells suggest that PSCs participate in the development of pancrea s fibrosis.