Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages.
OBJECTIVE
Mesenchymal stem cells (MSCs) are capable of modulating the immune system through interaction with a wide range of immune cells. This study investigates the hypothesis that interaction of MSCs with macrophages could play a significant role in their antiinflammatory/immune modulatory effects.


METHODS
MSCs were derived from bone marrow and monocytes were isolated from peripheral blood of healthy donors. We cultured human monocytes for 7 days without any added cytokines to generate macrophages, and then cocultured them for 3 more days with culture-expanded MSCs. We used cell surface antigen expression and intracellular cytokine expression patterns to study the immunophenotype of macrophages at the end of this coculture period, and phagocytic assays to investigate their functional activity in vitro.


RESULTS
Macrophages cocultured with MSCs consistently showed high-level expression of CD206, a marker of alternatively activated macrophages. Furthermore, these macrophages expressed high levels of interleukin (IL)-10 and low levels of IL-12, as determined by intracellular staining, typical of alternatively activated macrophages. However, macrophages cocultured with MSCs also expressed high levels of IL-6 and low levels of tumor necrosis factor-alpha (TNF-alpha) compared to controls. Functionally, macrophages cocultured with MSCs showed a higher level of phagocytic activity.


CONCLUSIONS
We describe a novel type of human macrophage generated in vitro after coculture with MSCs that assumes an immunophenotype defined as IL-10-high, IL-12-low, IL-6-high, and TNF-alpha-low secreting cells. These MSC-educated macrophages may be a unique and novel type of alternatively activated macrophage with a potentially significant role in tissue repair.
Kim
Jaehyup
J
Department of Medicine, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI 53705-2275, USA.
Hematti
Peiman
P
D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D010586:Phagocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12