Mesenchymal stem cells promote macrophage polarization toward M2b-like cells

Kudlik, Gyöngyi and Hegyi, Beáta and Czibula, Ágnes and Monostori, Éva and Buday, László and Uher, Ferenc (2016) Mesenchymal stem cells promote macrophage polarization toward M2b-like cells. EXPERIMENTAL CELL RESEARCH, 348 (1). pp. 36-45. ISSN 0014-4827

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Abstract

Mesenchymal stem or stromal cells (MSCs) act on different components of the immune response including macrophages (MPhis). Therefore this study has been committed to explore how MSCs may modify the effect of MPhi polarization upon an inductive environment using mouse bone marrow (BM)-derived "naive", unpolarized MPhis. Phagocytosis of various MPhi subtypes was different since M1 and M2b showed poorer, while M2a higher rate of phagocytosis. MSCs significantly promoted yeast ingestion by M1 and M2b and diminished it by M2a cells. Under polarizing conditions, MSCs profoundly affected the TNFalpha production of MPhi subtypes since M1 and M2b MPhis produced less and M2a produced higher amount of TNFalpha while the amount of IL-10 was not affected. The most striking effect of MSCs was registered on M2b cells since the inflammatory TNFalpha dominance remarkably shifted to the immunosuppressive IL-10. Prepolarized M1 cells readily converted to M2a and M2b states when polarizing conditions changed from M1 to M2a or M2b induction, respectively. Repolarizing from M1 to M2a resulted in the decline of IL-10 and TNFalpha and defined elevation of Ym1 similar to levels characteristic to M2a primarily polarized from naive BM-MPhis. Similarly, polarization of M1 to M2b MPhis was successful showing increase in IL-10 and reduction in TNFalpha levels characteristic to M2b cells. However, when co-culturing with MSCs, M1-M2a or M1-M2b transition was not affected. Crosstalk between MPhis and MSCs depended on PGE-2 since COX-2 inhibition reduced the effect of MSCs to establish an IL-10-dominant cytokine production by MPhis.

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