4.5 Article

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

期刊

STEM CELLS AND DEVELOPMENT
卷 27, 期 9, 页码 579-589

出版社

MARY ANN LIEBERT, INC
DOI: 10.1089/scd.2017.0196

关键词

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

资金

  1. Sanquin Research [PPOC13-030P]
  2. Landsteiner Foundation for Blood Transfusion Research [1014, 1101]
  3. Intramural Research Program of the NIH, National Cancer Institute

向作者/读者索取更多资源

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-). However, it remains unknown whether IFN- can also influence hematopoietic support by BM-MSCs. In this study, we elucidate the impact of IFN- on the hematopoietic support of BM-MSCs. We found that IFN- increases expression of interleukin (IL)-6 and stem cell factor by human BM-MSCs. IFN--treated BM-MSCs drive HSPCs toward myeloid commitment in vitro, but impair subsequent differentiation of HSPC. Moreover, IFN--ARE-Del mice with increased IFN- production specifically lose their BM-MSCs, which correlates with a loss of hematopoietic stem cells' quiescence. Although IFN- treatment enhances the immunomodulatory function of MSCs in a clinical setting, we conclude that IFN- negatively affects maintenance of BM-MSCs and their hematopoietic support in vitro and in vivo.

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