TY - JOUR
T1 - Interferon-gamma impairs maintenance and alters hematopoietic support of bone marrow mesenchymal stromal cells
AU - Goedhart, Marieke
AU - Cornelissen, Anne S.
AU - Kuijk, Carlijn
AU - Geerman, Sulima
AU - Kleijer, Marion
AU - van Buul, Jaap D.
AU - Huveneers, Stephan
AU - Raaijmakers, Marc H. G. P.
AU - Young, Howard A.
AU - Wolkers, Monika C.
AU - Voermans, Carlijn
AU - Nolte, Martijn A.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85046551574&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29649408
U2 - https://doi.org/10.1089/scd.2017.0196
DO - https://doi.org/10.1089/scd.2017.0196
M3 - Article
C2 - 29649408
SN - 1547-3287
VL - 27
SP - 579
EP - 589
JO - Stem cells and development
JF - Stem cells and development
IS - 9
ER -