Adipose Tissue-Derived Stem Cells As A Regenerative Therapy ... : Hepatology (original) (raw)

Liver Injury and Regeneration

Adipose Tissue-Derived Stem Cells As A Regenerative Therapy for A Mouse Steatohepatitis-Induced Cirrhosis Model

Seki, Akihiro1,2,*; Sakai, Yoshio1,3,*; Komura, Takuya2; Nasti, Alessandro2; Yoshida, Keiko2; Higashimoto, Mami2; Honda, Masao1; Usui, Soichiro2; Takamura, Masayuki2; Takamura, Toshinari2; Ochiya, Takahiro4; Furuichi, Kengo5; Wada, Takashi3; Kaneko, Shuichi1,2

1_Department of Gastroenterology, Kanazawa University Hospital, Ishikawa, Japan_

2_Disease Control and Homeostasis, Kanazawa University, Ishikawa, Japan_

3_Department of Laboratory Medicine, Kanazawa University Hospital, Ishikawa, Japan_

4_National Cancer Research Institute, Tokyo, Japan_

5_Division of Blood Purification, Kanazawa University Hospital, Ishikawa, Japan_

Received 27 September 2012; Accepted 15 April 2013

Address reprint requests to: Shuichi Kaneko, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8641, Japan. E-mail: [email protected]; fax: +81-76-234-4250.

Potential conflict of interest: Nothing to report.

Supported in part by subsidies from the Japanese Ministry of Education, Culture, Sports, Science and Technology and the Japanese Ministry of Health, Labor and Welfare.

These authors contributed equally to this work.

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. (Hepatology 2013;53:1133–1142)