Systematic analysis of the effects of hepatocyte transplantation on rats with acute liver failure.

Abstract

BACKGROUND/AIMS: Acute liver failure either after liver resection or as part of underlying liver disease is still associated with high mortality. Hepatocyte transplantation in various forms has attracted attention recently. However, none of those reports have investigated the thorough and systematic analysis of effect of hepatocyte transplantation on acute liver failure induced by 90% hepatectomy. Therefore, we investigated systematic analysis of effect of hepatocyte transplantation on rats with acute liver failure.

METHODOLOGY: Male Sprague-Dawley rats were used. Group I rats (n = 26) received intrasplenic injection of 2 x 10(7) hepatocytes in 0.3 mL Dulbecco's modified Eagle's medium (DMEM) 24 hours prior to 90% hepatectomy. Group II rats (n = 24) received intrasplenic injection of DMEM only. Twenty-two rats from group I and 20 from group II were observed for the determination of survival time. The remaining 8 (4/each group) rats were used to assess the liver function and regeneration.

RESULTS: The hepatocyte bearing spleen revealed active glucose-6-phosphatase activity. In group I rats, the survival was longer and that group had more long-term survivors than those of group II controls. In group I, there was significant increase in the ratio of weight of remnant liver lobes to body weight. At 24 hours after hepatectomy, group I rats had improved biochemical parameters compared to those of group II rats.

CONCLUSIONS: In rats with acute liver failure, intrasplenic hepatocyte transplantation acts as a bridge to support experimental rats from acute liver failure to liver regeneration, prolong survival in rats with acute liver failure and improve biochemical parameters.