Ultrastructure, enzymatic, and transport properties of the PICM-19 bipotent liver cell line

The pig epiblast-derived PICM-19 cell line was previously shown to spontaneously differentiate into liver-like cells and structures and to secrete serum proteins. A study was undertaken to further define the liver-like characteristics of the PICM-19 cell line. PICM-19 cells displayed in vitro ultrastructure, enzymatic, and transport characteristics similar to those of parenchymal hepatocytes and bile duct epithelium. The PICM-19 cells contained large oval nuclei, numerous oval to elongate mitochondria with flat cristae, extensive rough and smooth endoplasmic reticulum, Golgi complexes, lipid vacuoles, and glycogen granules. Biliary canaliculi with intraluminal projecting microvilli were delimited by the junctional apparatuses between adjacent PICM-19 cells. The PICM-19 cells rapidly transported fluorescein into their biliary canaliculi from the extracellular environment. PICM-19 cells that had differentiated into multicellular ductal structures had high gamma-glutamyltranspeptidase (GGT) activity at their apical surfaces as shown by histochemical staining. PICM-19 total GGT activity was at least 19 times higher than that found in porcine hepatocytes. Metyrapone induced cytochrome P-450 content of PICM-19 cells was at least one-fourth of that found in porcine hepatocytes. PICM-19 P-450 activity induced by 7-ethoxycoumarin was nearly equivalent to that of primary cultures of pig hepatocytes. The data support the proposal that differentiated PICM-19 cells resembled hepatocytes, or bile duct epithelium cells, and, therefore, the PICM-19 cell line behaved like early embryonic liver progenitor cells.