Adipose tissue-derived stem cells as a regenerative therapy for a mouse steatohepatitis-induced cirrhosis model.

Abstract

UNLABELLED: Cirrhosis is a chronic liver disease that impairs hepatic function and causes advanced fibrosis. Mesenchymal stem cells have gained recent popularity as a regenerative therapy since they possess immunomodulatory functions. We found that injected adipose tissue-derived stem cells (ADSCs) reside in the liver. Injection of ADSCs also restores albumin expression in hepatic parenchymal cells and ameliorates fibrosis in a nonalcoholic steatohepatitis model of cirrhosis in mice. Gene expression analysis of the liver identifies up- and down-regulation of genes, indicating regeneration/repair and anti-inflammatory processes following ADSC injection. ADSC treatment also decreases the number of intrahepatic infiltrating CD11b(+) and Gr-1(+) cells and reduces the ratio of CD8(+) /CD4(+) cells in hepatic inflammatory cells. This is consistent with down-regulation of genes in hepatic inflammatory cells related to antigen presentation and helper T-cell activation. CONCLUSION: These results suggest that ADSC therapy is beneficial in cirrhosis, as it can repair and restore the function of the impaired liver.