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Stem Cells Dev. 2018 May 1;27(9):579-589. doi: 10.1089/scd.2017.0196. Epub 2018 Apr 16.

Interferon-Gamma Impairs Maintenance and Alters Hematopoietic Support of Bone Marrow Mesenchymal Stromal Cells.

Author information

1
1 Sanquin Research and Landsteiner Laboratory, Department of Hematopoiesis, Academic Medical Center, University of Amsterdam , Amsterdam, Netherlands .
2
2 Sanquin Research and Landsteiner Laboratory, Department of Molecular Cell Biology, Academic Medical Center, University of Amsterdam , Amsterdam, Netherlands .
3
3 Department of Hematology and Erasmus Stem Cell Institute, Erasmus MC Cancer Institute , Rotterdam, Netherlands .
4
4 Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute , Frederick, Maryland.

Abstract

Bone marrow (BM) mesenchymal stromal cells (MSCs) provide microenvironmental support to hematopoietic stem and progenitor cells (HSPCs). Culture-expanded MSCs are interesting candidates for cellular therapies due to their immunosuppressive and regenerative potential which can be further enhanced by pretreatment with interferon-gamma (IFN-γ). However, it remains unknown whether IFN-γ can also influence hematopoietic support by BM-MSCs. In this study, we elucidate the impact of IFN-γ on the hematopoietic support of BM-MSCs. We found that IFN-γ increases expression of interleukin (IL)-6 and stem cell factor by human BM-MSCs. IFN-γ-treated BM-MSCs drive HSPCs toward myeloid commitment in vitro, but impair subsequent differentiation of HSPC. Moreover, IFN-γ-ARE-Del mice with increased IFN-γ production specifically lose their BM-MSCs, which correlates with a loss of hematopoietic stem cells' quiescence. Although IFN-γ treatment enhances the immunomodulatory function of MSCs in a clinical setting, we conclude that IFN-γ negatively affects maintenance of BM-MSCs and their hematopoietic support in vitro and in vivo.

KEYWORDS:

HSC; MSC; bone marrow; interferon-gamma; support

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