Xeno-repopulation of Fah^(-/-)Nod/Scid mice livers by human hepatocytes  

作　　者：SU BaoLiang LIU ChangCheng XIANG Dao ZHANG HaiBin YUAN SiMing WANG MinJun CHEN Fei ZHU HaiYing HE ZhiYing WANG Xin HU YiPing 

机构地区：[1]Department of Cell Biology, Second Military Medical University, Shanghai 200433, China [2]Center for Instrumental Analysis, China Pharmaceutical University, Nanjing 210009, China [3]Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China [4]Department of Plastic Surgery, Nanjing General Hospital of Nanjing Military Command, Nanjing 210002, China [5]Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

出　　处：《Science China(Life Sciences)》2011年第3期227-234,共8页中国科学（生命科学英文版）

基　　金：supported by the National High Technology Research and Development Program of China(Grant No. 2006AA02Z474);the National Natural Science Foundation of China(Grant No. 30801115);the China Postdoctoral Science Foundation(Grant No. 20070410743);the National Basic Research Program of China(Grant No. 2010CB945600)

摘　　要：Functional human hepatocytes xenografted into the liver of mice can be used as a model system to study pharmacokinetics,infection of hepatitis viruses,and the efficacy of hepatitis vaccines.Significant levels of liver xeno-repopulation have been reported in Fah-/-Rag2-/-Il2rg-/-mice.However,the high mortality and low breeding rate of this model may hinder its application.A new model,termed Fah-/-Nod/Scid mice,which combines the advantages of liver repopulation in Fah-/-mice with the ease of xenotransplantation in Nod/Scid mice was obtained by gradual cross-breeding.Fah-/-Nod/Scid mice were easily maintained in breeding colonies and in adult animal care facilities.FK506 treatment combined with gradual withdrawal of NTBC before cell transplantation ensured that Fah-/-Nod/Scid mice were susceptible to liver xeno-repopulation by human hepatocytes;the proportion of engrafted human hepatocytes reached 33.6%.The function of the expanded human hepatocytes within the chimeric liver was confirmed by weight curve analysis,the expression of characteristic proteins,and the biochemical analysis of liver function.These results show that Fah-/-Nod/Scid mice are an ideal humanized liver mouse model with many useful applications.Functional human hepatocytes xenografted into the liver of mice can be used as a model system to study pharmacokinetics,infection of hepatitis viruses,and the efficacy of hepatitis vaccines.Significant levels of liver xeno-repopulation have been reported in Fah^-/-Rag2^-/-Il2rg^-/-mice.However,the high mortality and low breeding rate of this model may hinder its application.A new model,termed Fah^-/-Nod/Scid mice,which combines the advantages of liver repopulation in Fah^-/-mice with the ease of xenotransplantation in Nod/Scid mice was obtained by gradual cross-breeding.Fah^-/-Nod/Scid mice were easily maintained in breeding colonies and in adult animal care facilities.FK506 treatment combined with gradual withdrawal of NTBC before cell transplantation ensured that Fah^-/-Nod/Scid mice were susceptible to liver xeno-repopulation by human hepatocytes;the proportion of engrafted human hepatocytes reached 33.6%.The function of the expanded human hepatocytes within the chimeric liver was confirmed by weight curve analysis,the expression of characteristic proteins,and the biochemical analysis of liver function.These results show that Fah^-/-Nod/Scid mice are an ideal humanized liver mouse model with many useful applications.

关 键 词：human hepatocyte humanized liver cell transplantation Fah gene knockout mice Nod/Scid mice 

分 类 号：S828[农业科学—畜牧学] Q95-331[农业科学—畜牧兽医]