Effects of Hepatic Stimulatory Factor Released from Free or Microencapsulated Hepatocytes on Galactosamine Induced Fulminant Hepatic Failure Animal Model

Abstract

This paper describes the presence of a cell free hepatocyte stimulating factor secreted by hepatocyte cultures. Hepatocytes were isolated from 70-90 grams Wistar-Lewis rats. Free or microencapsulated hepatocytes in alginate matrix were cultured separately. Cell free supernatant was collected from the culture medium in which was cultured free hepatocytes; microencapsulated hepatocytes or control microcapsules containing no microcapsules. This was tested in the galactosamine rats. A galactosamine dose of 2.7 g/Kg of body weight given intraperitoneally to Wistar-Lewis rats resulted in reproducible hepatic necrosis with 90% mortality. Cell free supernatant from one day old free hepatocyte cultures was able to increase survival time and incorporation of 3H-thymidine in liver of galactosamine induced fulminant hepatic failure rats at the time of maximal liver damage. The cell free supernatant of one day old microencapsulated hepatocyte cultures did not have the same stimulatory effect either on survival time or incorporation of thymidine. Another study was carried out as follows. The microcapsules containing hepatocytes were ruptured. The supernatant of the microcapsule contents was collected. This was found to have hepatic stimulatory effect as shown by survival time and incorporation of thymidine. This suggests that hepatocytes are a source of a factor(s) which is capable of stimulating liver regeneration in the galactosamine induced fulminant hepatic failure rats at the time of maximal liver damage. Since the molecular weight cut off of this particular preparation of microcapsule is molecular larger than albumin, this suggests that the molecular weight of this factor is in the macromolecular range.