Abstract
Pediatric liver transplantation has become increasingly successful, but donor scarcity is a major limitation. We studied fetal liver-cell transplantation as an alternative to provide functional hepatic replacement and evaluated the efficacy of the intraperitoneal (i.p.) transplantation of fetal liver cells in the treatment of acute hepatic failure in rats. Outbred Wistar rat fetuses (18–20 days' gestation) were used as donors. In Wistar male rats (250–300 g), acute hepatic failure was achieved by simultaneous portacaval shunt and 70% hepatectomy. This model produced lethal hepatic failure in a highly reproducible manner. Fetal liver cells were isolated by the mechanical method. Group A consisted of 2×107 fetal liver cells suspended in 1 ml phosphate-buffered saline (PBS) while group B consisted of only 1 ml PBS. Both were injected i.p. just after surgery. Fetal liver-cell transplantation (group A) significantly improved survival. The degree of hypoglycemia was significantly less significant 1 day after surgery in group A and the levels of plasma insulin and glucagon 3 days after surgery were significantly lower in group A than in group B. The results indicate that i.p. transplantation of fetal liver cells can provide metabolic support in rats.
Similar content being viewed by others
References
Aiken J, Cima L, Schloo B, Schloo B, Mooney D, Langer R, Vacanti JP (1990) Studies in rat liver perfusion for optimal harvest of hepatocytes. J Pediatr Surg 25: 140–145
Bumgardner GL, Fasola C, Sutherland DER (1988) Prospects for hepatocyte transplantation. Hepatology 8: 1158–1161
Cuervas-mons V, Cienfuegos JA, Maganto P, Eroles G, Castillo-Oliveres J, Segovia de Arana JM (1984) Time-related efficacy of liver cell isografts in fulminant hepatic failure. Transplantation 38: 23–25
Demetriou AA, Reisner A, Sanchez J, Levenson SM, Moscioni AD, Chowdhury JR (1988) Transplantation of microcarrier-attached hepatocytes into 90% partially hepatectomized rats. Hepatology 8: 1006–1009
Emond JC, Thistlethwait WJR, Alonso EM, Alonso EM, Bloelsh CE (1989) Reduce-size orthotopic liver transplantation: use in the management of children with chronic liver disease. Hepatology 10: 867–872
Greco AV, Crucitti F, Ghirlanda G, Manna R, Altomonte L, Rebuzzi AG, Bertoli A (1979) Insulin and glucagon concentrations in portal and peripheral veins in patients with hepatic cirrhosis. Diabetologia 17: 23–28
Itatsu T, Kishimoto T, Shintani T, Ukai M (1979) The release and metabolism of pancreatic hormones after major hepatectomy in the dog. Endocrinol Jpn 26: 319–324
Lucarelli G, Fliedner TM, Gale RP (1980) Fetal liver transplantation: current concepts and future directions. Excerpta Medica, Amsterdam Oxford Princeton, pp 247–302
Makowka L, Rotstein LE, Falk RE, Falk JA, Zuk R, Langer B, Blendis LM, Phillips MJ (1981) Studies into the mechanism of reversal of experimental acute hepatic failure by hepatocyte transplantation 1. Can J Surg 24: 39–44
Minato M, Houssin D, Morin J, Gigou M, Szekely AM (1982) Surgically induced acute hepatic failure in the rat. Eur Surg Res 14: 185–191
Nakamura T, Nishizawa T, Hagiya M, Seki T, Shimonishi M, Sugimura A, Tashiro K, Shimizu S (1989) Molecular cloning and expression of human hepatocyte growth factor. Nature 342: 440–443
Pringault E, Plas C (1983) Differences in degradation processes for its receptor in cultured foetal hepatocytes. Biochem J 212: 529–537
Shurberg JL, Resnick RH, Koff RS, Ros E, Baum RA, Pallotta JA (1977) Serum lipids, insulin, and glucagon after portacaval shunt in cirrhosis. Gastroenterology 72: 301–304
Sutherland DER, Numata M, Matas AJ, Simmons RL, Najarian JS (1977) Hepatocellular transplantation in acute liver failure. Surgery 82: 124–132
Tsuji K, Moriya K, Akiyama M (1985) Experimental study of fetal liver transplantation. Tokai J Exp Clin Med 10: 225–232
Author information
Authors and Affiliations
Additional information
Correspondence to: Y. Hata
Rights and permissions
About this article
Cite this article
Hata, Y., Hase, T., Yoshikawa, Y. et al. Fetal liver-cell transplantation for surgically-induced acute hepatic failure in rats. Pediatr Surg Int 8, 23–26 (1993). https://doi.org/10.1007/BF02352995
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02352995