| First Author | Goedhart M | Year | 2018 |
| Journal | Stem Cells Dev | Volume | 27 |
| Issue | 9 | Pages | 579-589 |
| PubMed ID | 29649408 | Mgi Jnum | J:313663 |
| Mgi Id | MGI:6791274 | Doi | 10.1089/scd.2017.0196 |
| Citation | Goedhart M, et al. (2018) Interferon-Gamma Impairs Maintenance and Alters Hematopoietic Support of Bone Marrow Mesenchymal Stromal Cells. Stem Cells Dev 27(9):579-589 |
| abstractText | 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-gamma). However, it remains unknown whether IFN-gamma can also influence hematopoietic support by BM-MSCs. In this study, we elucidate the impact of IFN-gamma on the hematopoietic support of BM-MSCs. We found that IFN-gamma increases expression of interleukin (IL)-6 and stem cell factor by human BM-MSCs. IFN-gamma-treated BM-MSCs drive HSPCs toward myeloid commitment in vitro, but impair subsequent differentiation of HSPC. Moreover, IFN-gamma-ARE-Del mice with increased IFN-gamma production specifically lose their BM-MSCs, which correlates with a loss of hematopoietic stem cells' quiescence. Although IFN-gamma treatment enhances the immunomodulatory function of MSCs in a clinical setting, we conclude that IFN-gamma negatively affects maintenance of BM-MSCs and their hematopoietic support in vitro and in vivo. |
