The CD45+ fraction in murine adipose tissue-derived stromal cells harbor 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 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.

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