Immunodeficient Mice - A Suitable Model For Cell Transplantation In Non-Alcoholic Steatohepatisis (Nash)

NASH is a benign disease and will progress, if untreated, into fibrosis/cirrhosis and potentially into HCC. Human cell therapy approaches for the treatment of NASH have not been addressed yet. The present work aimed at establishing an animal model to evaluate the feasibility of stem cell‐derived hepatocytes. Immunodeficient Pfp/Rag2 −/− mice were fed a methionin‐cholin‐deficient diet (MCD diet) up to 5 weeks. Alanine aminotransferase (ALT) and triglycerides were determined in the serum. Histological analyses of liver sections were performed to detect structural abnormalities by HE, the collagen distribution by sirius‐red and fat depositions by sudan III staining. Expression of the acute phase protein SAA, the proinflammatory cytokine TNFα, the marker for activated stellate cells αSMA as well as collagen1 in liver tissue were specified by RT‐PCR. Already 3 weeks after feeding the MCD diet, microsections displayed a deteriorated architecture of the liver tissue, which worsened with continued feeding. By HE‐staining massive steatosis and hepatocellular injury were observed and confirmed by sudan III staining in livers of animals fed the MCD diet as compared to animals fed the control diet. Fibrosis in livers of animals on MCD diet was obvious by collagen staining. The marker of hepatocyte fade ALT was significantly higher (2‐fold) in the serum of mice on MCD diet. Serum triglycerides were significantly lower in MCD diet‐fed animals. RT‐PCR analysis revealed elevated mRNA levels of SAA and TNFα as well as of αSMA and collagen1 in the livers of mice fed the MCD diet. Thus, immunodeficient Pfp/Rag2 mice fed with the MCD diet displayed typical features of NASH, which makes this animal model suitable to evaluate pre‐clinically human cell therapy approaches of liver diseases.