Effects of intraperitoneal transplantation of microcarrier-attached hepatocytes on D-galactosamine-induced acute liver failure in rats.
A study was conducted to investigate morphologic as well as metabolic characteristics of microcarrier-attached hepatocytes in culture, and also to evaluate the effect of intraperitoneal transplantation of the microcarrier-attached hepatocytes on acute hepatic failure in rats induced by D-galactosamine (GalN). Rat hepatocytes were isolated by collagenase perfusion, and cultured on collagen-coated microcarriers. Protein synthesis estimated by [14C] leucine incorporation was four-fold higher in microcarrier culture than in cell suspension. The rates of albumin, transthyretin and bile acid syntheses in hepatocytes cultured on microcarriers were similar to those in monolayer culture. When microcarrier-attached hepatocytes were intraperitoneally transplanted into rats with Galn-induced acute liver failure, a marked improvement in survival rate was observed as compared with control rats which received injections of microcarriers alone (80% vs 0% beyond 6 days of transplantation). Mean serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), methionine and glucose levels were similar in both groups, while serum bilirubin and ammonia levels were lower (P less than 0.1, P less than 0.05) in rats transplanted with the microcarrier-attached hepatocytes. Immunohistochemical examinations revealed that the transplanted hepatocytes around microcarriers had albumin synthesis activity, whereas almost no albumin synthesis was demonstrated in recipient liver. In conclusion, intraperitoneal transplantation of the microcarrier-attached hepatocytes will provide sufficient metabolic support, representing detoxication of ammonia (and presumably bilirubin) and synthesis of albumin, to allow GalN-damaged liver function to restore. Microcarrier culture of isolated hepatocytes seems to be one of the most appropriate tools for an artificial liver support.
First Department of Internal Medicine, Gifu University School of Medicine, Japan.
M
M
Nagaki
T
T
Kano
Y
Y
Muto
T
T
Yamada
H
H
Ohnishi
H
H
Moriwaki
D000208:Acute Disease; D000418:Albumins / Q000096:biosynthesis; D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D003911:Dextrans / Q000008:administration & dosage*; D005688:Galactosamine; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D008107:Liver Diseases / Q000601:surgery*; D016031:Liver Transplantation / Q000379:methods; D008297:Male; D008863:Microspheres; D010529:Peritoneal Cavity; D011228:Prealbumin / Q000096:biosynthesis; D051381:Rats
D000418:Albumins; D001647:Bile Acids and Salts; D003911:Dextrans; D011228:Prealbumin; D005688:Galactosamine; C052839:Cytodex