MOUSE PANCREATIC ACINAR DUCTULAR TISSUE GIVES RISE TO EPITHELIAL CULTURES THAT ARE MORPHOLOGICALLY, BIOCHEMICALLY, AND FUNCTIONALLY INDISTINGUISHABLE FROM INTERLOBULAR DUCT CELL-CULTURES/

Most of the pancreatic exocrine epithelium consists of acinar and intr alobular duct (ductular) cells, with the balance consisting of interlo bular and main duct cells. Fragments of mouse acinar/ductular epitheli um can be isolated by partial digestion with collagenase and purified by Ficoll density gradient centrifugation. We investigated whether pre viously developed culture conditions used for duct epithelium would re sult in the selective survival and proliferation of ductular cells fro m the acinar/ductular fragments. The fragments were cultured on nitroc ellulose filters coated with extracellular matrix. After 2 to 4 wk the filters were covered with proliferating cells resembling parallel cul tures of duct epithelium by the following criteria: protein/DNA ratio, light and electron microscopic appearance, the presence of duct marke rs (carbonic anhydrase [CA] activity, CA II mRNA, the cystic fibrosis transmembrane conductance regulator), the near absence of acinar cell markers (amylase and chymotrypsin), a similar polypeptide profile afte r sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the p resence of spontaneous and secretin-stimulated electrogenic ion transp ort. Both duct and ductular epithelia formed fluid-filled cysts in col lagen gels and both could be subcultured. We conclude that acinar/duct ular tissue gives rise to ductular cells in culture by some combinatio n of acinar cell death and/or transdifferentiation to a ductular pheno type, accompanied by proliferation of these cells and preexisting duct ular cells. These cultures may be used to investigate the properties o f this part of the pancreatic duct system, from which most of the panc reatic juice water and electrolytes probably originates.