Cell-free supernatant from hepatocyte cultures improves survival of rats with chemically induced acute liver failure.

Abstract Current support or replacement therapies for fulminant hepatic failure are frequently inadequate. Hepatocyte transplantation has been found to permit or facilitate recovery from chemically induced liver failure in rats. The mechanisms are unclear, but function of the transplanted cells or stimulation of host liver regeneration by factors released from the cells could improve survival; there is evidence from experiments by other investigators using cell fractions to support the latter hypothesis. We compared intact cells and the supernatant from cultured liver cells for their influence on the survival of Fischer male rats with d -galactosamine ( d -Gal) induced acute liver failure (ALF). All treatments were given 20 to 24 hr after poisoning. Cell supernates were injected intrasplenically (sp), intraperitoneally (ip), or intravenously (iv). Liver cells (2 × 10 7 ) suspended in Hanks' solution were injected intrasplenically. Untreated rats and rats treated with Hanks' solution or culture medium alone had a 94–100% mortality, with all deaths occurring between 38 and 74 hr after poisoning. Improved survival was seen in all experimental groups: 47% of the rats receiving intact liver cells survived; 50, 55, and 62% of the rats receiving cell-free supernate by the sp, ip, or iv routes, respectively, survived. A chronologic electron micrographic study of livers from rats serially sacrificed in parallel experiments showed that recovery from morphological changes induced by d -Gal occurred in treated rats. These studies demonstrate that intact hepatocytes are not required to improve survival in rats with drug-induced ALF. Improved survival may be achieved by factors liberated by cultured hepatocytes that enhance the regeneration of the damaged liver. Supernatant from cultured liver cells may have a therapeutic potential in acute hepatic failure.