Mesenchymal Stromal Cells and Natural Killer Cells: A Complex Story of Love and Hate

Author(s): Mehdi Najar, Mohammad Fayyad-Kazan*, Makram Merimi, Arsène Burny, Dominique Bron, Hussein Fayyad-Kazan, Nathalie Meuleman, Laurence Lagneaux.

Journal Name: Current Stem Cell Research & Therapy

Volume 14 , Issue 1 , 2019

Become EABM
Become Reviewer

Abstract:

Mesenchymal stromal cells (MSCs), characterized by both multidifferentiation potential and potent immunomodulatory capacity, represent a promising, safe and powerful cell based-therapy for repairing tissue damage and/or treating diseases associated with aberrant immune responses. Natural killer (NK) cells are granular lymphocytes of the innate immune system that function alone or in combination with other immune cells to combat both tumors and virally infected cells. After their infusion, MSCs are guided by host inflammatory elements and can interact with different immune cells, particularly those of the innate immune system. Although some breakthroughs have been achieved in understanding these interactions, much remains to be determined. In this review, we discuss the complex interactions between NK cells and MSCs, particularly the importance of improving the therapeutic value of MSCs.

Keywords: Mesenchymal stromal cells, natural killer cells, immunomodulation, cellular cytotoxicity, natural killer receptors, cytokines.

[1]
Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8: 315-7.
[2]
Pittenger MF. Multilineage Potential of Adult Human Mesenchymal Stem Cells. Science (80- ) 1999; 284: 143-7.
[3]
Najar M, Krayem M, Meuleman N, Bron D, Hélène B, Lagneaux L. Immunohematology Mesenchymal Stromal Cell-based Therapy. Appl Immunohistochem Mol Morphol 2017; 1.
[4]
Spaggiari GM, Moretta L. Interactions between mesenchymal stem cells and dendritic cells. Adv Biochem Eng Biotechnol 2013; 130: 199-208.
[5]
Kim J, Hematti P. Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages. Exp Hematol 2009; 37: 1445-53.
[6]
Duffy MM, Ritter T, Ceredig R, Griffin MD. Mesenchymal stem cell effects on T-cell effector pathways. Stem Cell Res Ther 2011; 2: 34.
[7]
Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105: 1815-22.
[8]
Ghannam S, Pène J, Moquet-Torcy G, Torcy-Moquet G, Jorgensen C, Yssel H. Mesenchymal stem cells inhibit human Th17 cell differentiation and function and induce a T regulatory cell phenotype. J Immunol 2010; 185: 302-12.
[9]
Corcione A, Benvenuto F, Ferretti E, et al. Human mesenchymal stem cells modulate B-cell functions. Blood 2006; 107: 367-72.
[10]
Franquesa M, Mensah FK, et al. Human adipose tissue-derived mesenchymal stem cells abrogate plasmablast formation and induce regulatory B cells independently of T helper cells. Stem Cells 2015; 33: 880-91.
[11]
Thomas H, Jäger M, Mauel K, Brandau S, Lask S, Flohé SB. Interaction with Mesenchymal Stem Cells Provokes Natural Killer Cells for Enhanced IL-12/IL-18-Induced Interferon-Gamma Secretion. Mediators Inflamm 2014; 2014: 1-11.
[12]
Dunavin N, Dias A, Li M, McGuirk J. Mesenchymal stromal cells: What is the mechanism in acute graft-versus-host disease? Biomedicines 2017; 5: 39.
[13]
Rasmusson I, Ringdén O, Sundberg B, Le Blanc K. Mesenchymal stem cells inhibit the formation of cytotoxic T lymphocytes, but not activated cytotoxic T lymphocytes or natural killer cells. Transplantation 2003; 76: 1208-13.
[14]
Sotiropoulou PA, Perez SA, Gritzapis AD, Baxevanis CN, Papamichail M. Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells 2006; 24: 74-85.
[15]
Baron F, Lechanteur C, Willems E, et al. Cotransplantation of mesenchymal stem cells might prevent death from Graft-Versus-Host Disease (GVHD) without abrogating graft-versus-tumor effects after HLA-mismatched allogeneic transplantation following nonmyeloablative conditioning. Biol Blood Marrow Transplant 2010; 16: 838-47.
[16]
Chieregato K, Albiero E, Castegnaro S, et al. A study on mutual interaction between cytokine induced killer cells and umbilical cord-derived mesenchymal cells: Implication for their in-vivo use. Blood Cells Mol Dis 2012; 49: 159-65.
[17]
Li Y, Qu YH, Wu YF, et al. Bone marrow mesenchymal stem cells suppressing activation of allogeneic cytokine-induced killer/natural killer cells either by direct or indirect interaction. Cell Biol Int 2015; 39: 435-45.
[18]
Chieregato K, Zanon C, Castegnaro S, et al. The cytotoxic action of the CD56+ fraction of cytokine-induced killer cells against a K562 cell line is mainly restricted to the natural killer cell subset. Blood Transfus 2016; 15: 93-100.
[19]
Hoogduijn MJ, Roemeling-van Rhijn M, Korevaar SS, Engela AU. weimar w, baan cc. immunological aspects of Allogeneic and autologous mesenchymal stem cell therapies. Hum Gene Ther 2011; 22: 1587-91.
[20]
Poggi A, Prevosto C, Massaro A-M, et al. Interaction between human NK cells and bone marrow stromal cells induces NK cell triggering: role of NKp30 and NKG2D receptors. J Immunol 2005; 175: 6352-60.
[21]
Jewett A, Arasteh A, Tseng HC, et al. Strategies to rescue Mesenchymal Stem Cells (MSCs) and Dental Pulp Stem Cells (DPSCs) from NK cell mediated cytotoxicity. PLoS One 2010; 5: 1-14.
[22]
Spaggiari GM, Capobianco A, Becchetti S, Mingari MC, Moretta L. Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation. Blood 2006; 107: 1484-90.
[23]
Götherström C, Lundqvist A, Duprez IR, Childs R, Berg L, le Blanc K. Fetal and adult multipotent mesenchymal stromal cells are killed by different pathways. Cytotherapy 2011; 13: 269-78.
[24]
Svirshchevskaya EV, Poltavtsev AM, Os’mak GZ, Poltavtseva RA. Activation of NK cells in mixed cultures of wharton’s jelly mesenchymal stromal cells and peripheral blood lymphocytes. Bull Exp Biol Med 2018; 164: 339-43.
[25]
Kaiserman D, Bird PI. Control of granzymes by serpins. Cell Death Differ 2010; 17: 586-95.
[26]
El Haddad N, Moore R, Heathcote D, et al. The novel role of SERPINB9 in cytotoxic protection of human mesenchymal stem cells. J Immunol 2011; 187: 2252-60.
[27]
Najar M, Fayyad-Kazan M, Meuleman N, Bron D, Fayyad-Kazan H, Lagneaux L. Mesenchymal stromal cells of the bone marrow and natural killer cells: Cell interactions and cross modulation. J Cell Commun Signal 2018.
[28]
Najar M, Fayyad-Kazan M, Meuleman N, Bron D, Fayyad-Kazan H, Lagneaux L. Immunomodulatory effects of foreskin mesenchymal stromal cells on natural killer cells. J Cell Physiol 2018.
[29]
Najar M, Fayyad-Kazan M, Meuleman N, Bron D, Fayyad-Kazan H, Lagneaux L. Immunological impact of Wharton’s Jelly mesenchymal stromal cells and natural killer cell co-culture. Mol Cell Biochem 2018.
[30]
Noone C, Kihm A, English K, O’Dea S, Mahon BP. IFN-γ stimulated human umbilical-tissue-derived cells potently suppress NK activation and resist NK-mediated cytotoxicity in vitro. Stem Cells Dev 2013; 22: 3003-14.
[31]
Giuliani M, Bennaceur-Griscelli A, Nanbakhsh A, et al. TLR ligands stimulation protects MSC from NK killing. Stem Cells 2014; 32: 290-300.
[32]
Chuang S-Y, Yang C-H, Chou C-C, Chiang Y-P, Chuang T-H, Hsu L-C. TLR-induced PAI-2 expression suppresses IL-1β processing via increasing autophagy and NLRP3 degradation. Proc Natl Acad Sci USA 2013; 110: 16079-84.
[33]
Bose K. Proteases in apoptosis : pathways, protocols and translational advances 2015.
[34]
Chatterjee D, Marquardt N, Tufa DM, et al. Role of gamma-secretase in human umbilical-cord derived mesenchymal stem cell mediated suppression of NK cell cytotoxicity. Cell Commun Signal 2014; 12: 63.
[35]
DelaRosa O, Sánchez-Correa B, Morgado S, et al. Human adipose-derived stem cells impair natural killer cell function and exhibit low susceptibility to natural killer-mediated lysis. Stem Cells Dev 2012; 21: 1333-43.
[36]
Pradier A, Passweg J, Villard J, Kindler V. Human bone marrow stromal cells and skin fibroblasts inhibit natural killer cell proliferation and cytotoxic activity. Cell Transplant 2011; 20: 681-91.
[37]
Zhao Z-G, Cao Z, Xu W, et al. Immune Protection Function of Multipotent Mesenchymal Stromal Cells: Role of Transforming Growth Factor-β1. Cancer Invest 2012; 30: 646-56.
[38]
Kyurkchiev D, Bochev I, Ivanova-Todorova E, et al. Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J Stem Cells 2014; 6: 552-70.
[39]
Giuliani M, Oudrhiri N. Human mesenchymal stem cells derived from induced pluripotent stem cells down-regulate NK-cell cytolytic machinery. Blood 2011; 118: 3254-62.
[40]
de Rham C, Ferrari-Lacraz S, Jendly S, Schneiter G, Dayer J-M, Villard J. The proinflammatory cytokines IL-2, IL-15 and IL-21 modulate the repertoire of mature human natural killer cell receptors. Arthritis Res Ther 2007; 9: R125.
[41]
Chatterjee D, Tufa DM, Baehre H, Hass R, Schmidt RE, Jacobs R. Natural killer cells acquire CD73 expression upon exposure to mesenchymal stem cells. Blood 2014; 123.
[42]
Lebbink RJ, Berg MCW van den, Ruiter T de, et al. The soluble Leukocyte-Associated Ig-Like Receptor (LAIR)-2 antagonizes the collagen/LAIR-1 inhibitory immune interaction. J Immunol 2008; 180: 1662-9.
[43]
Zeltz C, Gullberg D. The integrin-collagen connection - a glue for tissue repair? J Cell Sci 2016; 129.
[44]
Poggi A, Zocchi MR. NK cell autoreactivity and autoimmune diseases. Front Immunol 2014; 5: 27.
[45]
Perussia. The cytokine profile of resting and activated NK cells. Methods 1996; 9: 370-8.
[46]
Chatterjee D, Marquardt N, Tufa DM, et al. Human umbilical cord-derived mesenchymal stem cells utilize activin-a to suppress interferon-Î3 production by natural killer cells. Front Immunol 2014; 5: 662.
[47]
Ribeiro A, Laranjeira P, Mendes S, et al. Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells. Stem Cell Res Ther 2013; 4: 125-41.
[48]
Almeida CR, Vasconcelos DP, Gonçalves RM, Barbosa MA. Enhanced mesenchymal stromal cell recruitment via natural killer cells by incorporation of inflammatory signals in biomaterials. J R Soc Interface 2012; 9: 261-71.
[49]
Cuerquis J, Romieu-Mourez R, François M, et al. Human mesenchymal stromal cells transiently increase cytokine production by activated T cells before suppressing T-cell proliferation: Effect of interferon-γ and tumor necrosis factor-α stimulation. Cytotherapy 2014; 16: 191-202.
[50]
Wang L, Zhao Y, Liu Y, et al. IFN‐γ and TNF‐α synergistically induce mesenchymal stem cell impairment and tumorigenesis via NFκB signaling. Stem Cells 2013; 31: 1383-95.
[51]
Castro-Manrreza ME, Mayani H, Monroy-García A, et al. Human mesenchymal stromal cells from adult and neonatal sources: A comparative in vitro analysis of their immunosuppressive properties against T cells. Stem Cells Dev 2014; 23: 1217-32.
[52]
Abumaree MH, Bahattab E, Alsadoun A, et al. Characterization of the interaction between human decidua parietalis mesenchymal stem/stromal cells and natural killer cells. Stem Cell Res Ther 2018; 9: 102.
[53]
Agaugué S, Marcenaro E, Ferranti B, Moretta L, Moretta A. Human natural killer cells exposed to IL-2, IL-12, IL-18, or IL-4 differently modulate priming of naive T cells by monocyte-derived dendritic cells. Blood 2008; 112.
[54]
Consentius C, Akyüz L, Schmidt-Lucke JA, et al. Mesenchymal stromal cells prevent allostimulation in vivo and control checkpoints of th1 priming: migration of human DC to lymph nodes and NK Cell Activation. Stem Cells 2015; 33: 3087-99.
[55]
Cui R, Rekasi H, Hepner-Schefczyk M, Fessmann K, et al. Human mesenchymal stromal/stem cells acquire immunostimulatory capacity upon cross-talk with natural killer cells and might improve the NK cell function of immunocompromised patients. Stem Cell Res Ther 2016; 7: 88.
[56]
Casado JG, Tarazona R, Sanchez-Margallo FM NK. and MSCs Crosstalk: The Sense of Immunomodulation and Their Sensitivity. Stem Cell Rev Reports 2013; 9: 184-9.
[57]
Petri RM, Hackel A, Hahnel K, et al. Activated tissue-resident mesenchymal stromal cells regulate natural killer cell immune and tissue-regenerative function. Stem Cell Reports 2017; 280: 12239-45.
[58]
Krzewski K, Coligan JE. Human NK cell lytic granules and regulation of their exocytosis. Front Immunol 2012; 3.
[59]
Alter G, Malenfant JM, Altfeld M. CD107a as a functional marker for the identification of natural killer cell activity. J Immunol Methods 2004; 294: 15-22.
[60]
Bruno S, Grange C, Tapparo M, et al. Human liver stem cells suppress T-cell proliferation, NK activity, and dendritic cell differentiation. Stem Cells Int 2016; 2016: 8468549.
[61]
Blanco B, Herrero-Sánchez MC, Rodríguez-Serrano C, et al. Immunomodulatory effects of bone marrow versus adipose tissue derived mesenchymal stromal cells on NK cells: implications in the transplantation setting. Eur J Haematol 2016; 97: 528-37.
[62]
Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, Moretta L. Mesenchymal stem cells inhibit natural killer cell proliferation, cytotoxicity, and cytokine production : role of indoleamine 2, 3-dioxygenase and prostaglandin E2. Blood 2008; 111: 1327-33.
[63]
Voskoboinik I, Smyth MJ, Trapani JA. Perforin-mediated target-cell death and immune homeostasis. Nat Rev Immunol 2006; 6: 940-52.
[64]
Trapani JA, Trapani AJ. Immunity, granzymes and cell killing eLS. Chichester, UK: John Wiley & Sons, Ltd 2017; pp. 1-7.
[65]
Jacquemin G, Margiotta D, Kasahara A, et al. Granzyme B-induced mitochondrial ROS are required for apoptosis. Cell Death Differ 2015; 22: 862-74.
[66]
Martinvalet D, Zhu P, Lieberman J, Granzyme A. Induces Caspase-Independent Mitochondrial Damage, a Required First Step for Apoptosis. Immunity 2005; 22: 355-70.
[67]
Williams MS, Henkart PA. Do cytotoxic lymphocytes kill via reactive oxygen species? Immunity 2005; 22: 272-4.
[68]
Spaggiari GM, Capobianco A, Becchetti S, Mingari MC, Moretta L. Mesenchymal stem cell - natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2 - induced NK-cell proliferation. Blood 2006; 107: 1484-90.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 14
ISSUE: 1
Year: 2019
Page: [14 - 21]
Pages: 8
DOI: 10.2174/1574888X13666180912125736
Price: $58

Article Metrics

PDF: 21
HTML: 7
EPUB: 1