Morphologic Studies of Hepatocytes Entrapped in Hollow Fibers of a Bioartificial Liver

Abstract

A bioartificial liver cartridge was prepared by inoculating porcine hepatocytes into the inner space of hollow fibers of a hemodialyzer. The hepatocytes formed rod shaped cell aggregates during in vitro perfusion culture within 1 day. Morphologic examination was carried out on the aggregates by optical and electron microscopy. Each hepatocyte was in direct contact with adjacent cells and a bile canaliculus-like structure was occasionally seen between hepatocytes. High magnification observation showed that the canaliculus was separated from the remainder of the intercellular space by a tight junction. These facts suggest that the hepatocytes formed functionally associated cell aggregates with a compact morphology not unlike hepatocyte spheroids. These structures were well maintained for 7 days in culture, and then the amorphous area in the aggregates and the nonviable cell number increased with lengthening culture period. The bioartificial liver maintained the ability to metabolize lidocaine, ammonia, and galactose for 7 days and then deteriorated with time.