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Human Placental Mesenchymal Stem Cells (pMSCs) Play a Role as Immune Suppressive Cells by Shifting Macrophage Differentiation from Inflammatory M1 to Anti-inflammatory M2 Macrophages

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Abstract

Background

Mesenchymal stem cells (MSCs) have a therapeutic potential in tissue repair because of capacity for multipotent differentiation and their ability to modulate the immune response. In this study, we examined the ability of human placental MSCs (pMSCs) to modify the differentiation of human monocytes into macrophages and assessed the influence of pMSCs on important macrophage functions.

Methods

We used GM-CSF to stimulate the differentiation of monocytes into the M1 macrophage pathway and then co-cultured these cells with pMSCs in the early stages of macrophage differentiation. We then evaluated the effect on differentiation by microscopic examination and by quantification of molecules important in the differentiation and immune functions of macrophages using flow cytometry and ELISA. The mechanism by which pMSCs could mediate their effects on macrophage differentiation was also studied.

Results

The co-culture of pMSCs with monocytes stimulated to follow the inflammatory M1 macrophage differentiation pathway resulted in a shift to anti-inflammatory M2-like macrophage differentiation. This transition was characterized by morphological of changes typical of M2 macrophages, and by changes in cell surface marker expression including CD14, CD36, CD163, CD204, CD206, B7-H4 and CD11b, which are distinctive of M2 macrophages. Co-culture with pMSCs reduced the expression of the costimulatory molecules (CD40, CD80 and CD86) and increased the expression of co-inhibitory molecules (CD273, CD274 and B7-H4) as well as the surface expression of major histocompatibility complex (MHC-II) molecules. Furthermore, the secretion of IL-10 was increased while the secretion of IL-1β, IL-12 (p70) and MIP-1α was decreased; a profile typical of M2 macrophages. Finally, pMSCs induced the phagocytic activity and the phagocytosis of apoptotic cells associated with M2- like macrophages; again a profile typical of M2 macrophages. We found that the immunoregulatory effect of pMSCs on macrophage differentiation was mediated by soluble molecules acting partially via glucocorticoid and progesterone receptors.

Conclusions

We have shown that pMSCs can transition macrophages from an inflammatory M1 into an anti-inflammatory M2 phenotype. Our findings suggest a new immunosuppressive property of pMSCs that may be employed in the resolution of inflammation associated with inflammatory diseases and in tissue repair.

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Acknowledgments

We would also like to thank the staff and patients of the Delivery Unit, King Abdul Aziz Medical City for their help in obtaining placentae. This study was supported by grants from King Abdulla International Medical Research Centre (Grant No. RC08/114) and King Abdulaziz City for Science and Technology (Grant No. ARP-29-186). Bill Kalionis was supported by NHMRC Grant No. 509178.

Conflict of Interest

The authors declare no potential conflicts of interest

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Authors and Affiliations

  1. College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, National Guard Health Affairs, P.O. Box 22490, Riyadh, 11426, Mail Code 1515, Saudi Arabia

    M. H. Abumaree, M. A. Al Jumah, D. Jawdat, A. Al Khaldi, A. S. Fatani & B. A. Knawy

  2. King Abdullah International Medical Research Center, King Abdulaziz Medical City, National Guard Health Affairs, P.O. Box 22490, Riyadh, 11426, Mail Code 1515, Saudi Arabia

    M. H. Abumaree, M. A. Al Jumah, D. Jawdat, A. Al Khaldi, F. M. Abomaray & B. A. Knawy

  3. Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia, 3052

    B. Kalionis

  4. Department of Perinatal Medicine Pregnancy Research Centre, Royal Women’s Hospital, Parkville, Victoria, Australia, 3052

    B. Kalionis

  5. Department of Obstetrics & Gynaecology, Faculty of Medical and Health Sciences, University of Auckland, 11, Private Bag 92019, Grafton, Auckland, New Zealand

    L. W. Chamley

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  1. M. H. Abumaree
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  2. M. A. Al Jumah
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  3. B. Kalionis
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Correspondence to M. H. Abumaree.

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Abumaree, M.H., Al Jumah, M.A., Kalionis, B. et al. Human Placental Mesenchymal Stem Cells (pMSCs) Play a Role as Immune Suppressive Cells by Shifting Macrophage Differentiation from Inflammatory M1 to Anti-inflammatory M2 Macrophages. Stem Cell Rev and Rep 9, 620–641 (2013). https://doi.org/10.1007/s12015-013-9455-2

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