The Effects of Intrasplenic Transplantation of Hepatocytes on Rats with Acute Liver Failure Induced by a 90% Hepatectomy

Abstract

BACKGROUND: Acute liver failure either after liver resection or as part of underlying liver disease is still associated with high mortality. Various treatments have been tried to improve liver function during acute liver failure, including metabolic and nutritional support, hemodialysis, hemoperfusion, plasmapheresis, and hepatocyte and liver transplantation. Hepatocyte transplantation in various forms has attracted attention recently. We investigated whether allogeneic isolated hepatocytes transplanted in the spleen would prolong survival, facilitate liver regeneration, and improve biochemical parameters in rats with acute liver failure induced by a 90% hepatectomy. METHODS: Allogeneic male Sprague-Dawley rats were used. Group I rats (n=26) received an intrasplenic injection of 2 107 hepatocytes in 0.3 ml of Dulbecco's modified Eagle's medium (DMEM), and 1 days later acute liver failure was induced. Group II acute-liver-failure rats (n=24) received an intrasplenic injection of DMEM. The survival time was determined for 22 rats in Group I and for 20 rats in Group II. The remaining 8 (4/each group) acute liver failure rats were used to assess the liver function and regeneration. RESULTS: The survival was longer and the number of long-term survivors was greater for Group I rats than for the Group II controls. At 24 hour after the hepatectomy, Group I rats had lower ammonia, lower total bilirubin, lower activities of liver enzymes, and higher glucose levels than did Group II rats. In Group I, there was significant increase in the ratio of the weight of the remnant liver lobes to the body weight. CONCLUSION: Compared with the Control group intrasplenic hepatocyte transplantation in acute liver failure rats acts as a bridge to support experimental rats in going from acute or fulminant liver failureto liver regeneration or compensation, prolongs survival in rats with acute liver failure induced by a 90% hepatectomy, and improves the biochemical parameters, except for the albumin levels and prothrombin time. Transplantation of hepatocytes may be beneficial in supporting a liver which has been acutely devastated by a 90% hepatectomy.