The CD45+ fraction in murine adipose tissue derived stromal cells harbors immune‐inhibitory inflammatory cells

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 mes...

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Veröffentlicht in:European journal of immunology 2017-12, Vol.47 (12), p.2163-2174
Hauptverfasser: Nasti, Alessandro, Sakai, Yoshio, Seki, Akihiro, Buffa, Geraldine Belen, Komura, Takuya, Mochida, Hatsune, Yamato, Masatoshi, Yoshida, Keiko, Ho, Tuyen T. B., Takamura, Masayuki, Usui, Soichiro, Wada, Takashi, Honda, Masao, Kaneko, Shuichi
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Sprache:eng
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Zusammenfassung: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 10–20% of u‐ADSCs expressed the CD45 leukocyte‐related antigen. CD68, which is a marker of macrophages (MΦs), 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 MΦs. Genes related to M2‐type MUs 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 MΦs, contributed to the repair of liver tissue undergoing inflammation. Murine isolated uncultured adipose tissue derived stromal cells (u‐ADSCs) are valuable for regenerative therapy. They harbor CD45+ inhibitory M2‐type macrophage‐like cells, character confirmed by FACS and gene expression analysis. The CD45+ subset of u‐ADSCs has shown anti‐inflammatory properties in vitro and resulted therapeutically effective for acute hepatitis in mice.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.201646835