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
相关论文
共 72 条
  • [1] Mesenchymal stem cells: immune evasive, not immune privileged
    Ankrum, James A.
    Ong, Joon Faii
    Karp, Jeffrey M.
    [J]. NATURE BIOTECHNOLOGY, 2014, 32 (03) : 252 - 260
  • [2] Human Mesenchymal Stromal Cells Attenuate Graft-Versus-Host Disease and Maintain Graft-Versus-Leukemia Activity Following Experimental Allogeneic Bone Marrow Transplantation
    Auletta, Jeffery J.
    Eid, Saada K.
    Wuttisarnwattana, Patiwet
    Silva, Ines
    Metheny, Leland
    Keller, Matthew D.
    Guardia-Wolff, Rocio
    Liu, Chen
    Wang, Fangjing
    Bowen, Theodore
    Lee, Zhenghong
    Solchaga, Luis A.
    Ganguly, Sudipto
    Tyler, Megan
    Wilson, David L.
    Cooke, Kenneth R.
    [J]. STEM CELLS, 2015, 33 (02) : 601 - 614
  • [3] Mesenchymal Stromal Cells: Sensors and Switchers of Inflammation
    Bernardo, Maria Ester
    Fibbe, Willem E.
    [J]. CELL STEM CELL, 2013, 13 (04) : 392 - 402
  • [4] Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT)
    Bourin, Philippe
    Bunnell, Bruce A.
    Casteilla, Louis
    Dominici, Massimo
    Katz, Adam J.
    March, Keith L.
    Redl, Heinz
    Rubin, J. Peter
    Yoshimura, Kotaro
    Gimble, Jeffrey M.
    [J]. CYTOTHERAPY, 2013, 15 (06) : 641 - 648
  • [5] Briones Javier, 2011, Bone Marrow Res, V2011, P976793, DOI 10.1155/2011/976793
  • [6] Human Mesenchymal Stromal Cells from Adult and Neonatal Sources: A Comparative In Vitro Analysis of Their Immunosuppressive Properties Against T Cells
    Castro-Manrreza, Marta E.
    Mayani, Hector
    Monroy-Garcia, Alberto
    Flores-Figueroa, Eugenia
    Chavez-Rueda, Karina
    Legorreta-Haquet, Victoria
    Santiago-Osorio, Edelmiro
    Jose Montesinos, Juan
    [J]. STEM CELLS AND DEVELOPMENT, 2014, 23 (11) : 1217 - 1232
  • [7] A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells
    Chabannes, Dominique
    Hill, Marcelo
    Merieau, Emmanuel
    Rossignol, Julien
    Brion, Regis
    Soulillou, Jean Paul
    Anegon, Ignacio
    Cuturi, Maria Cristina
    [J]. BLOOD, 2007, 110 (10) : 3691 - 3694
  • [8] Human umbilical cord mesenchymal stem cells hUC-MSCs exert immunosuppressive activities through a PGE2-dependent mechanism
    Chen, Ke
    Wang, Ding
    Du, Wei Ting
    Han, Zhi-Bo
    Ren, He
    Chi, Ying
    Yang, Shao Guang
    Zhu, Delin
    Bayard, Francis
    Han, Zhong Chao
    [J]. CLINICAL IMMUNOLOGY, 2010, 135 (03) : 448 - 458
  • [9] Inflammatory conditions affect gene expression and function of human adipose tissue-derived mesenchymal stem cells
    Crop, M. J.
    Baan, C. C.
    Korevaar, S. S.
    IJzermans, J. N. M.
    Pescatori, M.
    Stubbs, A. P.
    van IJcken, W. F. J.
    Dahlke, M. H.
    Eggenhofer, E.
    Weimar, W.
    Hoogduijn, M. J.
    [J]. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2010, 162 (03) : 474 - 486
  • [10] Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli
    Di Nicola, M
    Carlo-Stella, C
    Magni, M
    Milanesi, M
    Longoni, PD
    Matteucci, P
    Grisanti, S
    Gianni, AM
    [J]. BLOOD, 2002, 99 (10) : 3838 - 3843