Bone marrow-derived mesenchymal stem cells propagate immunosuppressive/anti-inflammatory macrophages in cell-to-cell contact-independent and -dependent manners under hypoxic culture

• Published in: Experimental cell research 2017-09, Vol.358 (2), p.411-420
• Main Authors: Takizawa, Naoki, Okubo, Naoto, Kamo, Masaharu, Chosa, Naoyuki, Mikami, Toshinari, Suzuki, Keita, Yokota, Seiji, Ibi, Miho, Ohtsuka, Masato, Taira, Masayuki, Yaegashi, Takashi, Ishisaki, Akira, Kyakumoto, Seiko
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Bone Marrow - metabolism; Bone marrow cell culture; Cell adhesion; Cell Communication; Cell Differentiation - immunology; Cell Hypoxia; Cells, Cultured; Co-culture; Coculture Techniques; M2 macrophage; Macrophage Activation - physiology; Macrophages - immunology; Macrophages - metabolism; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mice; Monocytes/macrophages; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2017.07.014

Immunosuppressive/anti-inflammatory macrophage (Mφ), M2-Mφ that expressed the typical M2-Mφs marker, CD206, and anti-inflammatory cytokine, interleukin (IL)-10, is beneficial and expected tool for the cytotherapy against inflammatory diseases. Here, we demonstrated that bone marrow-derived lineage-positive (Lin+) blood cells proliferated and differentiated into M2-Mφs by cooperation with the bone marrow-derived mesenchymal stem cells (MSCs) under hypoxic condition: MSCs not only promoted proliferation of undifferentiated M2-Mφs, pre-M2-Mφs, in the Lin+ fraction via a proliferative effect of the MSCs-secreted macrophage colony-stimulating factor, but also promoted M2-Mφ polarization of the pre-M2-Mφs through cell-to-cell contact with the pre-M2-Mφs. Intriguingly, an inhibitor for intercellular adhesion molecule (ICAM)-1 receptor/lymphocyte function-associated antigen (LFA)-1, Rwj50271, partially suppressed expression of CD206 in the Lin+ blood cells but an inhibitor for VCAM-1 receptor/VLA-4, BIO5192, did not, suggesting that the cell-to-cell adhesion through LFA-1 on pre-M2-Mφs and ICAM-1 on MSCs was supposed to promoted the M2-Mφ polarization. Thus, the co-culture system consisting of bone marrow-derived Lin+ blood cells and MSCs under hypoxic condition was a beneficial supplier of a number of M2-Mφs, which could be clinically applicable to inflammatory diseases. [Display omitted] •Mesenchymal stem cells increase precursors of M2-macrophages under hypoxia.•ICAM-1/LFA-1 axis plays an important role on the M2-poralization.•Novel co-culture system was established to supply a number of M2-macrophages.