Original Articles
Copyright ©The Author(s) 2001. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 15, 2001; 7(3): 324-330
Published online Jun 15, 2001. doi: 10.3748/wjg.v7.i3.324
Transplantation of human hepatocytes into tolerized genetically immunocompetent rats
Edwin C. Ouyang, Catherine H. Wu, Cherie Walton, Kittichai Promrat, George Y. Wu
Edwin C. Ouyang, Catherine H. Wu, Cherie Walton, Kittichai Promrat, George Y. Wu, Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Rm. AM-045, 263 Farmington Avenue, Farmington, CT 06030.
Author contributions: All authors contributed equally to the work.
Correspondence to: George Y. Wu, MD, PhD, Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Rm. AM-045, 263 Farmington Avenue, Farmington, CT 06030. wu@nso.uchc.edu
Telephone: (860) 679-3158 Fax: (860) 679-3159
Received: April 11, 2001
Revised: April 19, 2001
Accepted: April 26, 2001
Published online: June 15, 2001
Abstract

AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression.

METHODS: Tolerance towards human hepatocytes was established by injection of primary human hepatocytes or Huh7 human hepatoma cells into the peritoneal cavities of fetal rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24 h after birth.

RESULTS: Mixed lymphocyte assays showed that spleen cells from non-tolerized rats were stimulated to proliferate when exposed to human hepatocytes, while cells from tolerized rats were not. Injections made between 15 d and 17 d of gestation produced optimal tolerizaton. Transplanted human hepatocytes in rat livers were visualized by immunohistochemical staining of human albumin. By dot blotting of genomic DNA in livers of tolerized rats 16 weeks after hepatocyte transplantation, it was found that approximately 2.5 × 105 human hepatocytes survived per rat liver. Human albumin mRNA was detected in rat livers by RT-PCR for 15 wk, and human albumin protein was also detectable in rat serum.

CONCLUSION: Tolerization of an immunocompetent rat can permit transplantation, and survival of functional human hepatocytes.

Keywords: liver/cytology, immune tolerance, cell transplantation