Crosstalk with Inflammatory Macrophages Shapes the Regulatory Properties of Multipotent Adult Progenitor Cells
Macrophages and microglia are key effector cells in immune-mediated neuroinflammatory disorders. Driving myeloid cells towards an anti-inflammatory, tissue repair-promoting phenotype is considered a promising strategy to halt neuroinflammation and promote central nervous system (CNS) repair. In this...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-01-01
|
| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2017/2353240 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850166478096039936 |
|---|---|
| author | Stylianos Ravanidis Jeroen F. J. Bogie Raf Donders Robert Deans Jerome J. A. Hendriks Piet Stinissen Jef Pinxteren Robert W. Mays Niels Hellings |
| author_facet | Stylianos Ravanidis Jeroen F. J. Bogie Raf Donders Robert Deans Jerome J. A. Hendriks Piet Stinissen Jef Pinxteren Robert W. Mays Niels Hellings |
| author_sort | Stylianos Ravanidis |
| collection | DOAJ |
| description | Macrophages and microglia are key effector cells in immune-mediated neuroinflammatory disorders. Driving myeloid cells towards an anti-inflammatory, tissue repair-promoting phenotype is considered a promising strategy to halt neuroinflammation and promote central nervous system (CNS) repair. In this study, we defined the impact of multipotent adult progenitor cells (MAPC), a stem cell population sharing common mesodermal origin with mesenchymal stem cells (MSCs), on the phenotype of macrophages and the reciprocal interactions between these two cell types. We show that MAPC suppress the secretion of tumor necrosis factor alpha (TNF-α) by inflammatory macrophages partially through a cyclooxygenase 2- (COX-2-) dependent mechanism. In turn, we demonstrate that inflammatory macrophages trigger the immunomodulatory properties of MAPC, including an increased expression of immunomodulatory mediators (e.g., inducible nitric oxide synthase (iNOS) and COX-2), chemokines, and chemokine receptors. Macrophage-primed MAPC secrete soluble factors that suppress TNF-α release by macrophages. Moreover, the MAPC secretome suppresses the antigen-specific proliferation of autoreactive T cells and the T cell stimulatory capacity of macrophages. Finally, MAPC increase their motility towards secreted factors of activated macrophages. Collectively, these in vitro findings reveal intimate reciprocal interactions between MAPC and inflammatory macrophages, which are of importance in the design of MAPC-based therapeutic strategies for neuroinflammatory disorders in which myeloid cells play a crucial role. |
| format | Article |
| id | doaj-art-da738969324c45e78720b1b6eefffb39 |
| institution | OA Journals |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-da738969324c45e78720b1b6eefffb392025-08-20T02:21:25ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/23532402353240Crosstalk with Inflammatory Macrophages Shapes the Regulatory Properties of Multipotent Adult Progenitor CellsStylianos Ravanidis0Jeroen F. J. Bogie1Raf Donders2Robert Deans3Jerome J. A. Hendriks4Piet Stinissen5Jef Pinxteren6Robert W. Mays7Niels Hellings8Biomedical Research Institute/Transnational University Limburg, School of Life Sciences, Hasselt University, 3590 Diepenbeek, BelgiumBiomedical Research Institute/Transnational University Limburg, School of Life Sciences, Hasselt University, 3590 Diepenbeek, BelgiumBiomedical Research Institute/Transnational University Limburg, School of Life Sciences, Hasselt University, 3590 Diepenbeek, BelgiumDepartment of Regenerative Medicine, Athersys Inc., Cleveland, OH, USABiomedical Research Institute/Transnational University Limburg, School of Life Sciences, Hasselt University, 3590 Diepenbeek, BelgiumBiomedical Research Institute/Transnational University Limburg, School of Life Sciences, Hasselt University, 3590 Diepenbeek, BelgiumReGenesys BVBA, Leuven, BelgiumDepartment of Regenerative Medicine, Athersys Inc., Cleveland, OH, USABiomedical Research Institute/Transnational University Limburg, School of Life Sciences, Hasselt University, 3590 Diepenbeek, BelgiumMacrophages and microglia are key effector cells in immune-mediated neuroinflammatory disorders. Driving myeloid cells towards an anti-inflammatory, tissue repair-promoting phenotype is considered a promising strategy to halt neuroinflammation and promote central nervous system (CNS) repair. In this study, we defined the impact of multipotent adult progenitor cells (MAPC), a stem cell population sharing common mesodermal origin with mesenchymal stem cells (MSCs), on the phenotype of macrophages and the reciprocal interactions between these two cell types. We show that MAPC suppress the secretion of tumor necrosis factor alpha (TNF-α) by inflammatory macrophages partially through a cyclooxygenase 2- (COX-2-) dependent mechanism. In turn, we demonstrate that inflammatory macrophages trigger the immunomodulatory properties of MAPC, including an increased expression of immunomodulatory mediators (e.g., inducible nitric oxide synthase (iNOS) and COX-2), chemokines, and chemokine receptors. Macrophage-primed MAPC secrete soluble factors that suppress TNF-α release by macrophages. Moreover, the MAPC secretome suppresses the antigen-specific proliferation of autoreactive T cells and the T cell stimulatory capacity of macrophages. Finally, MAPC increase their motility towards secreted factors of activated macrophages. Collectively, these in vitro findings reveal intimate reciprocal interactions between MAPC and inflammatory macrophages, which are of importance in the design of MAPC-based therapeutic strategies for neuroinflammatory disorders in which myeloid cells play a crucial role.http://dx.doi.org/10.1155/2017/2353240 |
| spellingShingle | Stylianos Ravanidis Jeroen F. J. Bogie Raf Donders Robert Deans Jerome J. A. Hendriks Piet Stinissen Jef Pinxteren Robert W. Mays Niels Hellings Crosstalk with Inflammatory Macrophages Shapes the Regulatory Properties of Multipotent Adult Progenitor Cells Stem Cells International |
| title | Crosstalk with Inflammatory Macrophages Shapes the Regulatory Properties of Multipotent Adult Progenitor Cells |
| title_full | Crosstalk with Inflammatory Macrophages Shapes the Regulatory Properties of Multipotent Adult Progenitor Cells |
| title_fullStr | Crosstalk with Inflammatory Macrophages Shapes the Regulatory Properties of Multipotent Adult Progenitor Cells |
| title_full_unstemmed | Crosstalk with Inflammatory Macrophages Shapes the Regulatory Properties of Multipotent Adult Progenitor Cells |
| title_short | Crosstalk with Inflammatory Macrophages Shapes the Regulatory Properties of Multipotent Adult Progenitor Cells |
| title_sort | crosstalk with inflammatory macrophages shapes the regulatory properties of multipotent adult progenitor cells |
| url | http://dx.doi.org/10.1155/2017/2353240 |
| work_keys_str_mv | AT stylianosravanidis crosstalkwithinflammatorymacrophagesshapestheregulatorypropertiesofmultipotentadultprogenitorcells AT jeroenfjbogie crosstalkwithinflammatorymacrophagesshapestheregulatorypropertiesofmultipotentadultprogenitorcells AT rafdonders crosstalkwithinflammatorymacrophagesshapestheregulatorypropertiesofmultipotentadultprogenitorcells AT robertdeans crosstalkwithinflammatorymacrophagesshapestheregulatorypropertiesofmultipotentadultprogenitorcells AT jeromejahendriks crosstalkwithinflammatorymacrophagesshapestheregulatorypropertiesofmultipotentadultprogenitorcells AT pietstinissen crosstalkwithinflammatorymacrophagesshapestheregulatorypropertiesofmultipotentadultprogenitorcells AT jefpinxteren crosstalkwithinflammatorymacrophagesshapestheregulatorypropertiesofmultipotentadultprogenitorcells AT robertwmays crosstalkwithinflammatorymacrophagesshapestheregulatorypropertiesofmultipotentadultprogenitorcells AT nielshellings crosstalkwithinflammatorymacrophagesshapestheregulatorypropertiesofmultipotentadultprogenitorcells |