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

Exp Cell Res. 2017 Sep 15;358(2):411-420. doi: 10.1016/j.yexcr.2017.07.014. Epub 2017 Jul 14.


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.

Keywords: Bone marrow cell culture; Cell adhesion; Co-culture; M2 macrophage; Mesenchymal stem cells; Monocytes/macrophages.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Bone Marrow / metabolism*
  • Cell Communication*
  • Cell Differentiation / immunology
  • Cell Hypoxia
  • Cells, Cultured
  • Coculture Techniques
  • Macrophage Activation / physiology*
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Mesenchymal Stem Cells / cytology*
  • Mice
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • Anti-Inflammatory Agents
  • Vascular Cell Adhesion Molecule-1