Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice

✍ Scribed by Isao Sakaida; Shuji Terai; Naoki Yamamoto; Koji Aoyama; Tsuyoshi Ishikawa; Hiroshi Nishina; Kiwamu Okita

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 552 KB
• Volume: 40
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.20452

✦ Synopsis

We investigated the effect of bone marrow cell (BMC) transplantation on established liver fibrosis. BMCs of green fluorescent protein (GFP) mice were transplanted into 4-week carbon tetrachloride (CCl 4 )-treated C57BL6 mice through the tail vein, and the mice were treated for 4 more weeks with CCl 4 (total, 8 weeks). Sirius red and GFP staining clearly indicated migrated BMCs existing along with fibers, with strong expression of matrix metalloproteinase (MMP)-9 shown by anti-MMP-9 antibodies and in situ hybridization. Double fluorescent immunohistochemistry showed the expression of MMP-9 on the GFPpositive cell surface. Film in situ zymographic analysis revealed strong gelatinolytic activity in the periportal area coinciding with the location of MMP-9 -positive BMCs. Four weeks after BMC transplantation, mice had significantly reduced liver fibrosis, as assessed by hydroxyproline content of the livers, compared to that of mice treated with CCl 4 alone. Subpopulation of Liv8-negative BMCs was responsible for this fibrolytic effect. In conclusion, mice with BMC transplants with continuous CCl 4 injection had reduced liver fibrosis and a significantly improved survival rate after BMC transplantation compared with mice treated with CCl 4 alone. This finding introduces a new concept for the therapy of liver fibrosis. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).