Transplantation of human hepatocytes into tolerized genetically immunocompetent rats

作     者：EdwinC.Ouyang CatherineH.Wu CherieWalton KittichaiPromrat GeorgeY.Wu 

作者机构：Department of MedicineDivision of Gastroenterology-HepatologyUniversity of Connecticut Health CenterRm. AM-045263 Farmington AvenueFarmingtonCT 06030 Correspondence to:George Y.Wu.M.D.Ph.D.Department of Medicine.Division of Gastroenterology-Hepatology.University of Connecticut I lealth CenterRm.AM-045.263 Farmington Avenue.FarmingtonC T 06030 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2001年第7卷第3期

页      面：324-330页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：National Institute of Diabetes and Digestive and Kidney Diseases  NIDDK  (R01DK042182) 

主　　题：Albumins Animals Cell Line, Transformed Disease Models, Animal Female Gene Expression Graft Survival Hepatitis Hepatoblastoma Hepatocytes Humans Immune Tolerance Immunocompetence Liver Liver Neoplasms Lymphocyte Culture Test, Mixed Microscopy, Confocal Pregnancy RNA, Messenger Rats Rats, Sprague-Dawley Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 

摘      要：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 24h 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 tolerization. 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 X 10(5) 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 immuno-competent rat can permit transplantation, and survival of functional human hepatocytes.