Abstract
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.
Highlights
Repair/regenerative therapy of impaired organs using stem cells has been a focus of research, while stem cells themselves have been investigated intensively [1]–[3]
Repair/regenerative therapy using cells freshly isolated from these tissues is preferable, as they are accessible and complicated procedures are not required to obtain cells enriched with mesenchymal stem cells (MSCs)
We observed that uncultured adipose tissue-derived stromal cells (u-ADSCs) were therapeutically beneficial to hepatitis as c-ADSCs were [20], and a part of its mechanism was contributed by the CD45+ subset of u-ADSCs; the CD45− subset of u-ADSCs were proven to contribute to therapeutic effect of u-ADSCs
Summary
Repair/regenerative therapy of impaired organs using stem cells has been a focus of research, while stem cells themselves have been investigated intensively [1]–[3]. MSCs are the ideal stem cells as they naturally reside in the adult body. They inhibit the immune system, which facilitates the repair and restoration of organs damaged by inflammation [4]–[6]. Bone marrow and adipose tissue are useful for repair/regenerative therapy as a feasible autologous source, since stromal cells in these tissues are naturally enriched in MSCs, avoiding advanced techniques for obtaining stem cells as of induced pluripotent stem cells [7],[8] and are not associated with serious ethical issues, such as the destruction of embryos for the establishment of ES cells. Subcutaneous adipose tissue is readily accessible to the aspiration of stromal cells enriched with MSCs [10]. Freshly isolated stromal cells are useful for the repair/regenerative therapy of damaged tissue [11]–[13]
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