Human hepatic regenerative stimulator substance: Partial purification and biological characterization of hepatic stimulator substance from human fetal liver cells

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Abstract
Current support or replacement therapies for fulminant acute hepatic failure are frequently very disappointing. In this study, human hepatic stimulator substance—a liver-specific growth factor—was partially purified from human fetal liver cells and characterized by its biological effects. Almost 70-fold protein content was purified with an approximately 80-fold increase in specific growth stimulator activity. Human hepatic stimulator substance proved to be heatstable, protase-sensitive, organ-specific and species-nonspecific. Human hepatic stimulator substance produced a two- to threefold increase of 3H-thymidine incorporation into hepatic DNA when injected intraperitoneally into growing weanling mice (nonhepatectomized) or regenerating rats (34% hepatectomy). The effects of hHSS in reversing the lethality of D-galactosamine (1.6 gm/kg body weight)—induced hepatic necrosis in rats were further evaluated. A survival rate of 4% (n = 24), 41% (n = 12, p < 0.05), 33% (n = 12, p < 0.05), 31% (n = 13, p < 0.05) and 18% (n = 11, p > 0.05) was observed when the rats were injected with 4 ml of saline intraperitoneally, 4 ml of human intact fetal hepatocytes (2.4 × 108) intraperitoneally, 4 ml of human hepatic stimulator substance intraperitoneally, 2 ml of twofold concentrated human hepatic stimulator substance intravenously and 1 ml of fourfold human hepatic stimulator substance intramuscularly, respectively, 20 hr after poisoning. These results suggested that human hepatic stimulator substance could successfully improve survival in rats with chemically induced acute liver failure by hepatocyte proliferation and might represent a significant potential for the management of clinical fulminant hepatic failure (HEPATOLOGY 1990;12:1144-1151).