Xeno-repopulation of Fah ??/sup> Nod/Scid mice livers by human hepatocytes

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• 作者：BaoLiang Su (1) (2)
  ChangCheng Liu (1)
  Dao Xiang (1)
  HaiBin Zhang (3)
  SiMing Yuan (4)
  MinJun Wang (1)
  Fei Chen (1)
  HaiYing Zhu (1)
  ZhiYing He (1)
  Xin Wang (5)
  YiPing Hu (1)
  
• 关键词：human hepatocyte ; humanized liver ; cell transplantation ; Fah gene knockout mice ; Nod/Scid mice
• 刊名：Science China Life Sciences
• 出版年：2011
• 出版时间：March 2011
• 年：2011
• 卷：54
• 期：3
• 页码：227-234
• 全文大小：679KB
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• 作者单位：BaoLiang Su (1) (2)
  ChangCheng Liu (1)
  Dao Xiang (1)
  HaiBin Zhang (3)
  SiMing Yuan (4)
  MinJun Wang (1)
  Fei Chen (1)
  HaiYing Zhu (1)
  ZhiYing He (1)
  Xin Wang (5)
  YiPing Hu (1)
  
  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
  

文摘

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 ??/sup> Rag2 ??/sup> Il2rg ??/sup> mice. However, the high mortality and low breeding rate of this model may hinder its application. A new model, termed Fah ??/sup> Nod/Scid mice, which combines the advantages of liver repopulation in Fah ??/sup> mice with the ease of xenotransplantation in Nod/Scid mice was obtained by gradual cross-breeding. Fah ??/sup> 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 ??/sup> 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 ??/sup> Nod/Scid mice are an ideal humanized liver mouse model with many useful applications.