These authors contributed equally to this work.
Liver Injury and Regeneration
Adipose tissue-derived stem cells as a regenerative therapy for a mouse steatohepatitis-induced cirrhosis model
Article first published online: 24 JUL 2013
© 2013 by the American Association for the Study of Liver Diseases
Volume 58, Issue 3, pages 1133–1142, September 2013
How to Cite
Seki, A., Sakai, Y., Komura, T., Nasti, A., Yoshida, K., Higashimoto, M., Honda, M., Usui, S., Takamura, M., Takamura, T., Ochiya, T., Furuichi, K., Wada, T. and Kaneko, S. (2013), Adipose tissue-derived stem cells as a regenerative therapy for a mouse steatohepatitis-induced cirrhosis model. Hepatology, 58: 1133–1142. doi: 10.1002/hep.26470
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.
- Issue published online: 29 AUG 2013
- Article first published online: 24 JUL 2013
- Accepted manuscript online: 17 MAY 2013 08:40AM EST
- Manuscript Accepted: 15 APR 2013
- Manuscript Received: 27 SEP 2012
Additional Supporting Information may be found in the online version of this article.
|hep26470-sup-0001-suppfig1.eps||1068K||Supporting Fig.1. Flow cytometry analysis of ADSC surface antigens. The inguinal adipose tissue of GFP-Tg mice was obtained, and the stromal cells were isolated and expanded for six passages in culture. The cells obtained were stained with (A) PE-labeled anti-CD90 or (B) anti-CD105 antibodies followed by flow cytometric analysis.|
|hep26470-sup-0002-suppfig2.eps||1347K||Supporting Fig. 2. Albumin expression in hepatic parenchymal cells. ADSCs from GFP-Tg mice (2 × 104) were injected twice every 2 weeks into the splenic subcapsule of cirrhotic C57Bl/6 mice fed the Ath+HF diet for 36 weeks. Control mice received PBS injections. Two weeks after the last injection, liver tissue was obtained and parenchymal cells were isolated for real-time PCR. Expression of (A) albumin and (B) AFP was normalized relative to GAPDH; *P < 0.05.|
|hep26470-sup-0003-suppfig3.eps||4345K||Supporting Fig. 3. Effect of ADSCs on collagen IV deposition in the cirrhotic liver. ADSCs from GFP-Tg mice (1 × 105) were injected twice every 2 weeks into the splenic subcapsule of cirrhotic C57Bl/6 mice fed an Ath+HF diet for 32 weeks. Control mice received PBS injections. (A) Two weeks after the last injection, liver tissue was obtained and stained with anti-collagen IV antibody. Scale bars = 100 µm. (B) The stained area was quantified using an image-analysis system. *P< 0.05.|
|hep26470-sup-0004-suppfig4.eps||731K||Supporting Fig. 4. Gene expression heat-map related to MMPs. ADSCs from GFP-Tg mice (1 × 105) were injected twice every 2 weeks into the splenic subcapsule of cirrhotic C57Bl/6 mice fed an Ath+HF diet for 40 weeks. Control mice received PBS injections. Two weeks later, liver tissue was subjected to RNA isolation and gene expression was assessed using DNA microarrays. One-way clustering analysis was performed on the obtained data of genes related to MMPs and a heat-map of the analysis is shown.|
|hep26470-sup-0005-suppfig5.eps||2352K||Supporting Fig. 5. Gene expression analysis of the CD4+T cell subpopulation of hepatic inflammatory cells. ADSCs from GFP-Tg mice (1 × 105) were injected twice every 2 weeks into the splenic subcapsule of C57Bl/6 mice fed an Ath+HF diet for 12 weeks (n=4). Control mice received PBS injections (n=4). Inflammatory cells were isolated from the liver, followed by separation of CD4+T cells, and gene expression was assessed by real-time PCR. IFN; interferon, TGF; tumor growth factor.|
|hep26470-sup-0006-supptab1.doc||42K||Table S1. Chemokine and cytokine-related genes whose expression in the hepatic inflammatory cells of NASH cirrhotic mice was significantly alterd by ADSC treatment.|
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