THE EFFECT OF SHORT-TERM HYPOXIC STRESS ON IMMUNOSUPPRESSIVE ACTIVITY OF PERIVASCULAR MULTIPOTENT STROMAL CELLS
Abstract
Multipotent mesenchymal stromal cells (MSCs) are stromal precursors with capacity to differentiate in osteo-, adipo-, and chondrodirections, participate in repair, regeneration and immune response. Those abilities, especially immunosuppression, make MSCs a perspective tool for cell therapy and regenerative medicine. Short-term hypoxic stress can occur in damaged tissues and negatively affect MSC capacities to modulate functions of activated peripheral blood mononuclear cells (PBMCs). In present paper, the impact of short-term hypoxic stress (<1% of oxygen) on immunosuppressive potential of tissue oxygen (5%) adapted MSCs was evaluated. At tissue oxygen level, we detected an increase of the ratio of innate immune cells (natural killers, NK) and a decrease of the ratio of adaptive immune cells (HLA-DR+ Т-cells) within floating PBMCs in the presence of MSCs. Additionally, inhibition of T-cell proliferation was observed.
Within adhered PBMCs the ratio of monocytes was higher and the ratio of NK-T-cells was lower.
Short-term hypoxic stress did not affect MSC immunosuppression toward lymphocytes in suspension.
Nevertheless, a decrease of percent of monocytes and NK-T-cells within adhered PBMCs was detected. Thus, hypoxic stress did not influence immunosuppressive activity of MSCs toward floating PBMCs. Attenuation of monocyte adhesion to MSCs upon cell-to-cell interaction may negatively impact on development of MSC-educated macrophages phenotype with anti-inflammatory activity. In vivo it may provoke slowdown of “response to injury” during inflammation.
About the Authors
K. V. ZornikovaRussian Federation
Horoshevskoye sh. 76A, Moscow, 123007, Russia;
Leninskiye gory 1–12, Moscow, 119234, Russia
Department of Cell Biology and Histology, Faculty of Biology
A. N. Gornostaeva
Russian Federation
Horoshevskoye sh. 76A, Moscow, 123007, Russia;
E. R. Andreeva
Russian Federation
Horoshevskoye sh. 76A, Moscow, 123007, Russia;
References
1. Murphy M.B., Moncivais K., Caplan A.I. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine // Exp. Mol. Med. 2013. Vol. 45. e54.
2. Murray I.R., West C.C., Hardy W.R., James A.W., Park T.S., Nguyen A., Tawonsawatruk T., Lazzari L., Soo C., P ault B. Natural history of mesenchymal stem cells, from vessel walls to culture vessels // Cell. Mol. Life Sci. 2014. Vol. 71. N 8. P. 1353–1374.
3. Jones B.J., McTaggart S.J. Immunosuppression by mesenchymal stromal cells: from culture to clinic // Exp. Hematol. 2008. Vol. 36. N 6. P. 733–741.
4. Benvenuto F., Ferrari S., Gerdoni E., Gualandi F., Frassoni F., Pistoia V., Mancardi G., Uccelli A. Human mesenchymal stem cells promote survival of T cells in a quiescent state // Stem Cells. 2007. Vol. 25. N 7. P. 1753–1760.
5. Di Nicola M., Carlo-Stella C., Magni M., Milanesi M., Longoni P.D., Matteucci P., Grisanti S., Gianni A.M. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli // Blood. 2002. Vol. 99. N 10. P. 3838–3843.
6. Kronsteiner B., Wolbank S., Peterbauer A., Hackl C., Redl H., van Griensven M., Gabriel C. Human mesenchymal stem cells from adipose tissue and amnion influence T-cells depending on stimulation method and presence of other immune cells // Stem Cells Dev. 2011. Vol. 20. N 12. Р. 2115–2126.
7. Engela A.U., Baan C.C., Dor F.J., Weimar W., Hoogduijn M.J. On the interactions between mesenchymal stem cells and regulatory T cells for immunomodulation in transplantation // Front. Immunol. 2012. Vol. 3. 126.
8. Gornostaeva A.N., Andreeva E.R., Buravkova L.B. Human MMSC immunosuppressive activity at low oxygen tension: direct cell-to-cell contacts and paracrine regulation // Human Physiology. 2013. Vol. 39. N 2. P. 136–146.
9. Corcione A., Benvenuto F., Ferreti E., Giunti D., Cappiello V., Cazzanti F., Risso M., Gualandi F., Mancardi G.L., Pistoia V., Uccelli A. Human mesenchymal stem cells modulate B-cell functions // Blood. 2006. Vol. 107. N 1. P. 367–372.
10. Krampera M., Cosmi L., Angeli R., Pasini A., Liotta F., Andreini A., Santarlasci V., Mazzinghi B., Pizzolo G., Vinante F., Romagnani P., Maggi E., Romagnani S., Annunziato F. Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells // Stem Cells. 2006. Vol. 24. N 2. P. 386–398.
11. Kim J., Hematti P. Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages // Exp. Hematol. 2009. Vol. 37. N 12. P. 1445–1453.
12. Melief S.M., Geutskens S.B., Fibbe W.E., Roelofs H. Multipotent stromal cells skew monocytes towards an antiinflammatory interleukin-10-producing phenotype by production of interleukin-6 // Haematologica. 2013. Vol. 98. N 6. P. 888–895.
13. Ivanovic Z. Hypoxia or in situ normoxia: The stem cell paradigm // J. Cell Physiol. 2009. Vol. 219. N 2. P. 271–275.
14. Buravkova L.B., Grinakovskaya O.S., Andreeva E.R., Zhambalova A.P., Kozionova M.P. Characteristics of human lipoaspirate-isolated mesenchymal stromal cells cultivated under lower oxygen tension // Cell Tiss. Biol. 2009. Vol. 3. N 1. P. 23–28.
15. Fotia C., Massa A., Boriani F., Baldini N., Granchi D. Hypoxia enhances proliferation and stemness of human adipose-derived mesenchymal stem cells // Cytotechnology. 2015. Vol. 67. N 6. P. 1073–1084.
16. Zuk P.A., Zhu M., Ashjian P., De Ugarte D.A., Huang J.I., Mizuno H., Alfonso Z.C., Fraser J.K., Benhaim P., Hedrick M.H. Human adipose tissue is a source of multipotent stem cells // Mol. Biol. Cell. 2002. Vol. 13. N 12. P. 4279–4295.
17. Parish C.R. Fluorescent dyes for lymphocyte migration and proliferation studies // Immunol. Cell Biol. 1999. Vol. 77. N 6. P. 499–508.
18. Glennie S., Soeiro I., Dyson P.J., Lam E.W., Dazzi F. Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells // Blood. 2005. Vol. 105. N 7. P. 2821–2827.
19. Gornostaeva A., Andreeva E., Buravkova L. Factors governing the immunosuppressive effects of multipotent mesenchymal stromal cells in vitro // Cytotechnology. 2016. Vol. 68. N 4. P. 565–577.
20. Ren G., Zhao X., Zhang L., Zhang J., L’Huillier A., Ling W., Roberts A.I., Le A.D., Shi S., Shao C., Shi Y. Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression // J. Immunol. 2010. Vol. 184. N 5. P. 2321–2328.
21. Hofmeyer K.A., Ray A., Zang X. The contrasting role of B7-H3 // Proc. Nat. Acad. Sci. U.S.A. 2008. Vol. 105. N 30. P. 10277–10278.
22. Espagnolle N., Balguerie A., Arnaud E., Sensebé L., Varin A. CD54-mediated interaction with pro-inflammatory macrophages increases the immunosuppressive function of human mesenchymal stromal cells // Stem Cell Reports. 2017. Vol. 8. N 4. P. 961–976
23. Andreeva E.R., Lobanova M.V., Udartseva O.O., Buravkova L.B. Response of adipose tissue-derived stromal cells in tissue-related О2 microenvironment to short-term hypoxic stress // Cells Tissues Organs. 2015. Vol. 200. N 5. P. 307–315.
Review
For citations:
Zornikova K.V., Gornostaeva A.N., Andreeva E.R. THE EFFECT OF SHORT-TERM HYPOXIC STRESS ON IMMUNOSUPPRESSIVE ACTIVITY OF PERIVASCULAR MULTIPOTENT STROMAL CELLS. Vestnik Moskovskogo universiteta. Seriya 16. Biologiya. 2018;73(1):16-21. (In Russ.)