Empowering the immune fate of bone marrow mesenchymal stromal cells: gene and protein changes

被引:12
作者
Najar, Mehdi [1 ]
Ouhaddi, Yassine [1 ]
Bouhtit, Fatima [2 ]
Melki, Rahma [2 ]
Afif, Hassan [1 ]
Boukhatem, Noureddine [2 ]
Merimi, Makram [2 ,3 ]
Fahmi, Hassan [1 ]
机构
[1] Univ Montreal, Osteoarthritis Res Unit, Univ Montreal Hosp Res Ctr CRCHUM, Dept Med, 900 St Denis,R11-424, Montreal, PQ H2X 0A9, Canada
[2] Univ Mohammed Premier, Lab Physiol Ethnopharmacol & Genet, Fac Sci, Oujda, Morocco
[3] Univ Libre Bruxelles, Inst Jules Bordet, Lab Expt Hematol, Brussels, Belgium
基金
加拿大健康研究院;
关键词
Bone marrow; Mesenchymal stromal cells; Immunomodulation; Regulatory mediators; Inflammation priming; VERSUS-HOST-DISEASE; LEUKEMIA INHIBITORY FACTOR; STEM-CELLS; LYMPHOCYTE-PROLIFERATION; INTERNATIONAL-SOCIETY; INTERFERON-GAMMA; TGF-BETA; EXPRESSION; MECHANISMS; CYTOKINE;
D O I
10.1007/s00011-018-1198-8
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Objective and designBone marrow mesenchymal stromal cells (BM-MSCs) are referred as a promising immunotherapeutic cell product. New approaches using empowered MSCs should be developed as for the treatment or prevention of different immunological diseases. Such preconditioning by new licensing stimuli will empower the immune fate of BM-MSCs and, therefore, promote a better and more efficient biological. Here, our main goal was to establish the immunological profile of BM-MSCs following inflammatory priming and in particular their capacity to adjust their immune-related proteome and transcriptome.Material and methodsTo run this study, we have used BM-MSC cell cultures, a pro-inflammatory cytokine cocktail priming, flow cytometry analysis, qPCR and ELISA techniques.ResultsDifferent expression levels of several immunological mediators such as COX-1, COX-2, LIF, HGF, Gal-1, HO-1, IL-11, IL-8, IL-6 and TGF- were constitutively observed in BM-MSCs. Inflammation priming substantially but differentially modulated the gene and protein expression profiles of these mediators. Thus, expressions of COX-2, LIF, HGF, IL-11, IL-8 and IL-6 were highly increased/induced and those of COX-1, Gal-1, and TGF- were reduced.ConclusionsCollectively, we demonstrated that BM-MSCs are endowed with a specific and modular regulatory machinery which is potentially involved in immunomodulation. Moreover, BM-MSCs are highly sensitive to inflammation and respond to such signal by properly adjusting their gene and protein expression of regulatory factors. Using such preconditioning may empower the immune fate of MSCs and, therefore, enhance their value for cell-based immunotherapy.
引用
收藏
页码:167 / 176
页数:10
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