5 years ago

The CD45+ fraction in murine adipose tissue-derived stromal cells harbor immune-inhibitory inflammatory cells

Tuyen T. B. Ho, Takashi Wada, Masatoshi Yamato, Masao Honda, Shuichi Kaneko, Keiko Yoshida, Geraldine Belen Buffa, Soichiro Usui, Masayuki Takamura, Hatsune Mochida, Takuya Komura, Yoshio Sakai, Akihiro Seki, Alessandro Nasti
Stromal cells in adipose tissue are useful for repair/regenerative therapy as they harbor a substantial number of mesenchymal stem cells; therefore, freshly isolated autologous uncultured adipose tissue-derived stromal cells (u-ADSCs) are useful for regenerative therapy, and obviate the need for mesenchymal stem cells. We evaluated the therapeutic effect of murine u-ADSCs and sorted subsets of u-ADSCs in a concanavalin A (ConA)-induced murine model of hepatitis, as well as their characteristics. We found that 10% to 20% of u-ADSCs expressed the CD45 leukocyte-related antigen. CD68, which is a marker of macrophages, was expressed by 50% of CD45+ u-ADSCs. About 90% of CD68+CD45+ cells expressed CD206 antigen, which is a marker of inhibitory M2-type macrophages. Genes related to M2-type macrophages were especially more highly expressed by CD45+CD206+ u-ADSCs than by CD45− u-ADSCs. CD45+ u-ADSCs inhibited the expression of cytokines/chemokines and suppressed the proliferation of splenocytes stimulated with ConA. We observed that not only whole u-ADSCs, but also the CD45+ subset of u-ADSCs ameliorated the ConA-induced hepatitis in mice. In conclusion we show that, freshly isolated murine u-ADSCs were effective against acute hepatitis, and CD45+ u-ADSCs acting phenotypically and functionally like M2-type macrophages, contributed to the repair of liver tissue undergoing inflammation. This article is protected by copyright. All rights reserved

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/eji.201646835

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