Immunomodulatory Effects of Multipotent Mesenchymal Stromal Cells on T-Cell Populations at Tissue-Related Oxygen Level
Authors: A. N. Gornostaeva, P. I. Bobyleva, E. R. Andreeva, L. B. Buravkova
Abstract:
Multipotent mesenchymal stromal cells (MSCs) possess immunomodulatory properties. The effect of MSCs on the crucial cellular immunity compartment – T-cells is of a special interest. It is known that MSC tissue niche and expected milieu of their interaction with T- cells are characterized by low oxygen concentration, whereas the in vitro experiments usually are carried out at a much higher ambient oxygen (20%). We firstly evaluated immunomodulatory effects of MSCs on T-cells at tissue-related oxygen (5%) after interaction implied cell-to-cell contacts and paracrine factors only. It turned out that MSCs under reduced oxygen can effectively suppress the activation and proliferation of PHAstimulated T-cells and can provoke decrease in the production of proinflammatory and increase in anti-inflammatory cytokines. In hypoxia some effects were amplified (inhibition of proliferation, antiinflammatory cytokine profile shift). This impact was more evident after direct cell-to-cell interaction; lack of intercellular contacts could revoke the potentiating effect of hypoxia.
Keywords: Cell-to-cell interaction, low oxygen, MSC immunosuppression, T-cells.
Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1096311
Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 1667References:
[1] D. Suva, J. Passweg, S. Arnaudeau, P. Hoffmeyer, and V. Kindler, "In vitro activated human T lymphocytes very efficiently attach to allogenic multipotent mesenchymal stromal cells and transmigrate under them”, J. Cell. Physiol, vol. 214, pp. 588–594, 2008.
[2] S. Tabera, J. A. Pérez-Simón, M. Díez-Campelo, L. I. Sánchez-Abarca, B. Blanco, A. López, et al., "The effect of mesenchymal stem cells on the viability, proliferation and differentiation of B-lymphocytes”, Haematologica, vol. 93, pp. 1301-1309, 2008.
[3] S. H. Yang, M. J. Park, I. H. Yoon, S. Y. Kim, S. H. Hong, J. Y. Shin, et al., "Soluble mediators from mesenchymal stem cells supress T cell proliferation by inducing IL-10”, Exp. Mol. Med., vol. 41, pp. 315-324, 2009.
[4] B. Kronsteiner, S. Wolbank, A. Peterbauer, C. Hackl, H. Redl, M. van Griensven, and C. Gabriel, "Human Mesenchymal Stem Cells from Adipose Tissue and Amnion Influence T-Cells Depending on Stimulation Method and Presence of Other Immune Cells”, Stem Cells And Development, vol. 20(12), pp. 2115-2126, 2011.
[5] B. Puissant, C. Barreau, P. Bourin, C. Clavel, J. Corre, C. Bousquet, et al., "Immunomodulatory effect of human adipose tissue-derived adult stem cells: comparison with bone marrow mesenchymal stem cells”, British Journal of Haematology, vol. 129, pp. 118–129, 2005.
[6] C. M. Kolf, E. Cho and R. S. Tuan, "Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation”, Arthrits Research & Therapy, vol. 9, pp. 204-214, 2007.
[7] L. B. Buravkova, O. S. Grinakovskaya, E. R. Andreeva, A. P. Jambalova, M. P. Kozionova, "Characteristics of mesenchymal stromal cells from human lipoaspirate cultured under reduced oxygen content”, Cytology, vol. 51(1), pp. 5-12, 2009
[8] W.L. Grayson, F. Zhao, B. Bunnell, and T. Ma, "Hypoxia enhances proliferation and tissue formation of human mesenchymal stem cells” Biochem Biophys Res Commun, vol. 358(3), pp. 948-953, 2007.
[9] C. Fehrer, R. Brunauer, G. Laschober, H. Unterluggauer, S. Reitinger, F. Kloss, et al., "Reduced oxygen tension attenuates differentiation capacity of human mesenchymal stem cells and prolongs their lifespan”, Aging Cell, vol. 6(6), pp. 745-757, 2007.
[10] U. Nekanti, S. Dastidar, P. Venugopal, S. Totey, and M. Ta, "Increased proliferation and analysis of differential gene expression in human wharton’s jelly-derived mesenchymal stromal cells under hypoxia” Cell, vol. 6(5), pp. 499-512, 2010.
[11] J. A. Krieger., J. C. Landsiedel, and D. A. Lawrence, "Differential in vitro effects of physiological and atmospheric oxygen tension on normal human peripheral blood mononuclear cell proliferation, cytokine and immunoglobulin production”. Int. J. Immunopharmacol, vol. 8(10), pp. 545-552, 1996.
[12] C. C. Caldwell, H. Kojima, D. Lukashev, J. Armstrong, M. Farber, S. G. Apasov, and M. V. Sitkovsky, "Differential Effects of Physiologically Relevant Hypoxic Conditions on T Lymphocyte Development and Effector Functions”, The Journal of Immunology, vol. 167, pp. 6140– 6149, 2001.
[13] L. Da Silva Meirelles, T. T. Sand, R. J. Harman, D. P. Lennon and A. I. Caplan, "MSC frequency correlates with blood vessel density in equine adipose tissue”, Tissue Eng Part A, vol. 15(2), pp. 221-229, 2009.
[14] Z. Li, H. Wei, L. Deng, X. Cong and X. Chen, "Expression and secretion of interleukin 1-beta, tumour necrosis factor alpha and interleukin 10 by hypoxia and serum deprivation-stimulated mesenchymal stem cells”, FEBS J, vol. 277(18), pp. 3688-3698, 2010.
[15] P. A. Zuk, M. Zhu, H. Mizuno, J. Huang, J. W. Futrell, A. J. Katz, et al., "Multilineage cells from human adipose tissue: implications for cellbased therapies”, Tissue Eng, vol. 7, pp. 211-218, 2001.
[16] K. Le Blanc, I. Rasmusson, C. Gotherstrom, C. Seidel, B. Sundberg, M. Sundin, et al., "Mesenchymal stem cells inhibit the expression of CD25 (Interleukin-2 Receptor) and CD38 on phytohaemagglutinin-activated lymphocytes”, Scandinavian Journal of Immunology, vol. 60, pp. 307– 315, 2004.
[17] S Cappellesso-Fleury, B. Puissant, P. A. Apoil, M. Titeux, P. Winterton, L. Casteilla, P. Bourin and A. Blancher, "Human fibroblasts share immunosuppressive properties with bone marrow mesenchymal stem cells”, J Clin Immunol, vol. 30, pp. 607–619, 2010.
[18] W Deng, Q. Han, L. Liao, S. You, H. Deng and R. C. Zhao, "Effects of allogeneic bone marrow-derived mesenchymal stem cells on T and B lymphocytes from BXSB mice”, DNA And Cell Biology, vol. 24(7), pp. 458–463, 2005.
[19] F. Saldanha-Araujo, R. Haddad, K. C. Farias, P. Souza Ade, P. V. Palma, A. G. Araujo, et al., "Mesenchymal stem cells promote the sustained expression of CD69 on activated T lymphocytes: roles of canonical and non-canonical NF-kB signaling”, J. Cell. Mol. Med., vol. 16(6), pp. 1232-1244, 2012.
[20] K. Le Blanc, "Mesenchymal stromal cells: Tissue repair and immune modulation”, Cytotherapy, vol. 8(6), pp. 559-561, 2006.
[21] A. J. Nauta and W. E. Fibbe, "Immunomodulatory properties of mesenchymal stromal cells”, Blood. vol. 110, pp. 3499-3506, 2007.
[22] G. Siegel, R. Schafer, and F. Dazzi, "The Immunosuppressive Properties of Mesenchymal Stem Cells”, Transplantation, vol. 87(9), pp. 45-49, 2009.
[23] M. Roemeling-van Rhijn, F. K. Mensah, S. S. Korevaar, M. J. Leijs, G. J. van Osch, J. N. Ijzermans, et al. "Effects of Hypoxia on the Immunomodulatory Properties of Adipose Tissue-Derived Mesenchymal Stem cells”, Front Immunol., vol. 18(4:203), Jul. 2013, doi: 10.3389/fimmu.2013.00203. eCollection 2013.
[24] S. Glennie, I. Soeiro, P. J. Dyson, E. W. Lam and F. Dazzi, "Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells”, Blood, vol. 105, pp. 2821-2827, 2005.
[25] K. Sato, K. Ozaki, I., Oh, A. Meguro, K. Hatanaka, T. Nagai et al., "Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells”, Blood, vol. 109(1), pp. 228–234, 2007.
[26] S.J. Prasanna, D. Gopalakrishnan, S.R. Shankar and A.B. Vasandan, "Pro-Inflammatory cytokines, IFNc and TNFa, influence immune properties of human bone marrow and wharton jelly mesenchymal stem cells differentially”, PLoS One, vol. 5, Iss. 2. - e9016, 2010.
[27] L. Jarvinen, L. Badri, S. Wettlaufer, T. Ohtsuka, T. J. Standiford, G. B. Toews, et al., "Lung resident mesenchymal stem cells isolated from human lung allografts inhibit T cell proliferation via a soluble mediator”, J Immunol., vol. 181(6), pp. 4389-4396, 2008.
[28] A. U. Engela, C. C. Baan, F. J. Dor, W. Weimar, M. J. Hoogduijn, "On the interactions between mesenchymal stem cells and regulatory T cells for immunomodulation in transplantation”, Front Immunol., vol. 3. pp. 126-134, 2012.
[29] A. Naldini and F. Carrar, "Hypoxia modulates cyclin and cytokine expression and inhibits peripheral mononuclear cell proliferation”, J Cell Physiol., vol. 181(3), pp. 448-454, 1999.
[30] J. Sun, Y. Zhang, M. Yang, Y. Zhang, Q. Xie, Z. Li, et al. "Hypoxia induces T-cell apoptosis by inhibiting chemokine C receptor 7 expression: the role of adenosine receptor A(2)”, Cell Mol Immunol., vol.7(1), pp. 77-82, 2010.
[31] M. Di Nicola, C. Carlo-Stella, M. Magni, M. Milanesi, P. D, Longoni, P. Matteucci, et al., "Human bone marrow stromal cells suppress Tlymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli”, Blood, vol. 99, pp. 3838-3843, 2002.
[32] Z. Selmani, A. Naji, I. Zidi, B. Favier, E. Gaiffe, L. Obert, et al., "Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4-CD25highFOXP3- regulatory T cells”, Stem Cells, vol. 26, pp. 212–222, 2008.
[33] R. Romieu-Mourez, M. Francois, M.N. Boivin., M. Bouchentouf, D. E. Spaner, J. Galipeau et al. "Cytokine modulation of TLR expression and activation in mesenchymal stromal cells leads to a proinflammatory phenotype”, J Immunol., vol. 182, pp. 7963–7973, 2009.
[34] R. S. Waterman., S. L. Tomchuck., S. L. Henkle and A. M. Betancourt, "A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an immunosuppressive MSC2 phenotype” PLoS One, vol. 5(4), - e10088, 2010
[35] Z. Selmani, A. Naji, E. Gaiffe, L. Obert, P. Tiberghien, N. Rouas-Freiss, et al., "HLA-G is a crucial immunosuppressive molecule secreted by adult human mesenchymal stem cells”, Transplantation, vol. 15(87), pp. 62-66, 2009.
[36] S. Aggarwal and M. F. Pittenger, "Human mesenchymal stem cells modulate allogeneic immune cell response”, Blood, vol. 105, pp. 1815- 1822, 2005.