Effect of Liver Cell Transplantation on Acute Hepatic Failure Induced by Massive Liver Resection in the Rat

  • Park, Jung-Hyun (Department of Surgery, Seoul St. Mary Hospital, The Catholic University of Korea) ;
  • Yoon, Young-Chul (Department of Surgery, Seoul St. Mary Hospital, The Catholic University of Korea) ;
  • Hong, Tae-Ho (Department of Surgery, Seoul St. Mary Hospital, The Catholic University of Korea) ;
  • You, Young-Kyoung (Department of Surgery, Seoul St. Mary Hospital, The Catholic University of Korea) ;
  • Kim, Dong-Goo (Department of Surgery, Seoul St. Mary Hospital, The Catholic University of Korea)
  • Published : 2011.05.30

Abstract

Purpose: This study is designed to ascertain the most effective quantity and injection route of hepatocytes in an acute liver failure model induced by massive liver resection in rats. Methods: Rats weighing 450 to 650 gm underwent partial hepatectomy that was 80% of their liver weight, resulting in acute liver failure. Hepatocytes were obtained by perfusing collagenase (Wako, Japan) solution through portal vein into liver of the allogenic rat. These hepatocytes were injected into different places with different dosage. The experimental groups were divided into the Control group, Splenic group I($2{\times}10^{6}$ cells into splenic capsule), Splenic group II($2{\times}10^{7}$ cells into splenic capsule), Portal vein group ($2{\times}10^{7}$ cells into portal vein), Subperitoneal group ($2{\times}10^{7}$ cells into subperitoneum). The experimental animals were observed carefully for 5 days for assessment of survival and regeneration of liver. Liver function tests including serum alanine aminotransferase (ALT), total bilirubin, gamma-glutamyl transferase (${\gamma}$-GTP) on postoperative 1, 2, 3, 5th days and histologic examinations of specimens obtained from each respective groups on postoperative 5th day were performed. Results: Serum ALT level on postoperative day 1 peaked and then gradually normalized showing statistical significance (p=0.035). Study groups showing statistically significant difference under repeated anova analysis were between the Splenic group II and Control (p=0.035), and between the Splenic group II and Portal vein group (p=0.001) with respect to serum ALT levels. Also, progression of each study group showed statistical significance. (p=0.02). Serum total bilirubin and r-GTP did not show any significant difference. Conclusion: Hepatocyte transplantation of $2{\times}10^{7}$ cells into spleen showed the best results in the acute hepatic failure rat.

Keywords

References

  1. Gill RQ, Sterling RK. Acute liver failure. J Clin Gastroenterol 2001;33:191-198. https://doi.org/10.1097/00004836-200109000-00005
  2. Gotthardt D, Riediger C, Weiss KH, et al. Fulminant hepatic failure: etiology and indications for liver transplantation. Nephrol Dial Transplant 2007;22 Suppl8:viii5-viii8. https://doi.org/10.1093/ndt/21.suppl_6.vi5
  3. Debray D, Yousef N, Durand P. New management options for end-stage chronic liver disease and acute liver failure: potential for pediatric patients. Paediatr Drugs 2006;8:1-13. https://doi.org/10.2165/00148581-200608010-00001
  4. Kjaergard LL, Liu J, Als-Nielsen B, Gluud C. Artificial and bioartificial support systems for acute and acute-on-chronic liver failure: a systematic review. JAMA 2003;289:217-222. https://doi.org/10.1001/jama.289.2.217
  5. Demetriou AA, Brown RS Jr, Busuttil RW, et al. Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure. Ann Surg 2004;239:660-667. https://doi.org/10.1097/01.sla.0000124298.74199.e5
  6. Bumgardner GL, Fasola C, Sutherland DE. Prospects for hepatocyte transplantation. Hepatology 1988;8:1158-1161. https://doi.org/10.1002/hep.1840080533
  7. Strom SC, Fisher RA, Thompson MT, et al. Hepatocyte transplantation as a bridge to orthotopic liver transplantation in terminal liver failure. Transplantation 1997;63:559-569. https://doi.org/10.1097/00007890-199702270-00014
  8. Higgins GM, Anderson RM. Experimental pathology of the liver. I. Restoration of the liver of the white rat following surgical removal. Arch Pathol 1931;12:186-202.
  9. Ostapowicz G, Fontana RJ, Schiødt FV, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 2002;137:947-954. https://doi.org/10.7326/0003-4819-137-12-200212170-00007
  10. Nardo B, Caraceni P, Puviani L, et al. Successful treatment of CCl4-induced acute liver failure with portal vein arterialization in the rat. J Surg Res 2006;135:394-401. https://doi.org/10.1016/j.jss.2006.03.032
  11. Tunon MJ, Alvarez M, Culebras JM, Gonzalez-Gallego J. An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure. World J Gastroenterol 2009;15:3086-3098. https://doi.org/10.3748/wjg.15.3086
  12. Fuller BJ. Transplantation of isolated hepatocytes. A review of current ideas. J Hepatol 1988;7:368-376. https://doi.org/10.1016/S0168-8278(88)80010-2
  13. Demetriou AA, Reisner A, Sanchez J, Levenson SM, Moscioni AD, Chowdhury JR. Transplantation of microcarrier-attached hepatocytes into 90% partially hepatectomized rats. Hepatology 1988;8:1006-1009. https://doi.org/10.1002/hep.1840080505
  14. Demetriou AA, Felcher A, Moscioni AD. Hepatocyte transplantation. A potential treatment for liver disease. Dig Dis Sci 1991;36:1320-1326. https://doi.org/10.1007/BF01307530
  15. Gabelein G, Nussler AK, Morgott F, et al. Intrasplenic or subperitoneal hepatocyte transplantation to increase survival after surgically induced hepatic failure? Eur Surg Res 2008;41:253-259. https://doi.org/10.1159/000140671
  16. He Y, Zhou J, Dou KF, Chen Y. A rat model for acute hepatic failure. Hepatobiliary Pancreat Dis Int 2003;2:423-425.
  17. Roger V, Balladur P, Honiger J, et al. A good model of acute hepatic failure: 95% hepatectomy. Treatment by transplantation of hepatocytes. Chirurgie 1996;121:470-473.
  18. Berry MN, Friend DS. High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study. J Cell Biol 1969;43:506-520. https://doi.org/10.1083/jcb.43.3.506
  19. Seglen PO. Preparation of isolated rat liver cells. Methods Cell Biol 1976;13:29-83.
  20. Groth CG, Arborgh B, Bjorken C, Sundberg B, Lundgren G. Correction of hyperbilirubinemia in the glucuronyltransferasedeficient rat by intraportal hepatocyte transplantation. Transplant Proc 1977;9:313-316.
  21. Hillan KJ, Burt AD, George WD, MacSween RN, Griffiths MR, Bradley JA. Intrasplenic hepatocyte transplantation in rats with experimental liver injury: morphological and morphometric studies. J Pathol 1989;159:67-73. https://doi.org/10.1002/path.1711590114
  22. Liu XL, Li LJ, Chen Z. Isolation and primary culture of rat hepatocytes. Hepatobiliary Pancreat Dis Int 2002;1:77-79.
  23. Gupta S, Rajvanshi P, Lee CD. Integration of transplanted hepatocytes into host liver plates demonstrated with dipeptidyl peptidase IV-deficient rats. Proc Natl Acad Sci U S A 1995;92:5860-5864. https://doi.org/10.1073/pnas.92.13.5860