Interferon-Gamma Impairs Maintenance and Alters Hematopoietic Support of Bone Marrow Mesenchymal Stromal Cells.
Interferon-Gamma Impairs Maintenance and Alters Hematopoietic Support of Bone Marrow Mesenchymal Stromal Cells.
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DOI：
10.1089/scd.2017.0196
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发表时间：
2018-05-01
影响因子：
4
通讯作者：
Nolte MA
中科院分区：
文献类型：
--
作者：
Goedhart M;Cornelissen AS;Kuijk C;Geerman S;Kleijer M;van Buul JD;Huveneers S;Raaijmakers MHGP;Young HA;Wolkers MC;Voermans C;Nolte MA
骨髓间充质基质细胞（MSCs）为造血干细胞和祖细胞（hspc）提供微环境支持。培养扩增的间充质干细胞具有免疫抑制和再生潜能，可以通过干扰素-γ (IFN-γ)预处理进一步增强，因此是细胞治疗的有趣候选者。然而，IFN-γ是否也能影响骨髓间充质干细胞的造血支持尚不清楚。在这项研究中，我们阐明了IFN-γ对骨髓间充质干细胞造血支持的影响。我们发现IFN-γ增加了人BM-MSCs中白细胞介素(IL)-6和干细胞因子的表达。IFN-γ处理的BM-MSCs在体外可驱动HSPC向髓系分化，但会损害HSPC的后续分化。此外，IFN-γ- are - del小鼠的IFN-γ产量增加，特异性地失去其BM-MSCs，这与造血干细胞的休眠丧失相关。尽管IFN-γ治疗在临床环境中增强了骨髓间充质干细胞的免疫调节功能，但我们得出结论，IFN-γ对骨髓间充质干细胞的维持及其体外和体内的造血支持产生负面影响。
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.
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影响因子：
12.8
作者：
Hodge DL;Berthet C;Coppola V;Kastenmüller W;Buschman MD;Schaughency PM;Shirota H;Scarzello AJ;Subleski JJ;Anver MR;Ortaldo JR;Lin F;Reynolds DA;Sanford ME;Kaldis P;Tessarollo L;Klinman DM;Young HA
通讯作者：
Young HA
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
影响因子：
5.2
作者：
Duque, Gustavo;Huang, Dao Chao;Kremer, Richard
通讯作者：
Kremer, Richard
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
20.3
作者：
de Bruin, Alexander M.;Demirel, Ozlem;Nolte, Martijn A.
通讯作者：
Nolte, Martijn A.