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.

bone marrow, HSC, interferon-gamma, MSC, support,
Stem Cells and Development

Goedhart, M. (Marieke), Cornelissen, A.S. (Anne S.), Kuijk, C. (Carlijn), Geerman, S. (Sulima), Kleijer, M. (Marion), van Buul, J.D, … Nolte, M.A. (2018). Interferon-gamma impairs maintenance and alters hematopoietic support of bone marrow mesenchymal stromal cells. Stem Cells and Development, 27(9), 579–589. doi:10.1089/scd.2017.0196