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

Hepatology. 2013 Sep;58(3):1133-42. doi: 10.1002/hep.26470. Epub 2013 Jul 24.

Abstract

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.

MeSH terms

  • Adipose Tissue / pathology*
  • Albumins / metabolism
  • Animals
  • CD11b Antigen / metabolism
  • CD4-CD8 Ratio
  • Cells, Cultured
  • Disease Models, Animal
  • Fatty Liver / complications*
  • Female
  • Liver Cirrhosis / etiology*
  • Liver Cirrhosis / therapy*
  • Liver Regeneration / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Chemokine / metabolism
  • Stem Cell Transplantation*
  • Stem Cells / pathology*
  • Treatment Outcome

Substances

  • Albumins
  • CD11b Antigen
  • Gr-1 protein, mouse
  • Receptors, Chemokine