SpringerLink
Log in

Insights into inflammatory priming of mesenchymal stromal cells: functional biological impacts

  • Review
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Mesenchymal stromal cells (MSCs) are multipotent adult cells with relevant biological properties making them interesting tools for cell-based therapy. These cells have the ability to home to sites of injury and secrete bioactive factors as part of their therapeutic functions. However, depending on the local environment, diverse functions of MSCs can be modulated and thus can influence their therapeutic value. The specific cytokine milieu within the site of inflammation is vital in determining the fate and cell behaviors of MSCs. Indeed, inflammatory signals (called as inflammatory priming), may induce critical changes on the phenotype, multilineage potential, hematopoietic support and immunomodulatory capacity of MSCs. Thus, for appropriate clinical application of MSCs, it is important to well know and understand these effects. In summary, investigating MSC interactions with the inflammatory environment is necessary to empower the therapeutic value of MSCs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Hass R, Kasper C, Böhm S, Jacobs R. Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal. 2011;9:12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8:315–7.

    Article  CAS  PubMed  Google Scholar 

  3. Michael S, Achilleos C, Panayiotou T, Strati K. Inflammation shapes stem cells and stemness during infection and beyond. Front Cell Dev Biol. 2016;4:118.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Fajardo-Orduña GR, Mayani H, Montesinos JJ. Hematopoietic support capacity of mesenchymal stem cells: biology and clinical potential. Arch Med Res. 2015;46:589–96.

    Article  PubMed  CAS  Google Scholar 

  5. Reinisch A, Etchart N, Thomas D, Hofmann NA, Fruehwirth M, Sinha S, et al. Epigenetic and in vivo comparison of diverse MSC sources reveals an endochondral signature for human hematopoietic niche formation. Blood. 2015;125:249–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Majumdar MK, Thiede MA, Haynesworth SE, Bruder SP, Gerson SL. Human marrow-derived mesenchymal stem cells (MSCs) express hematopoietic cytokines and support long-term hematopoiesis when differentiated toward stromal and osteogenic lineages. J Hematother Stem Cell Res. 2000;9:841–8.

    Article  CAS  PubMed  Google Scholar 

  7. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–7.

    Article  CAS  PubMed  Google Scholar 

  8. Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells—current trends and future prospective. Biosci Rep 2015;35:e00191.

  9. DiMarino AM, Caplan AI, Bonfield TL. Mesenchymal Stem Cells in Tissue Repair. Front. Immunol. 2013;4:201.

  10. ** J, Yan X, Zhou J, Yue W, Pei X. Mesenchymal stem cells in tissue repairing and regeneration: progress and future. Burns Trauma. 2013;1:13.

    Article  PubMed  Google Scholar 

  11. Fayyad-Kazan M, Fayyad-Kazan H, Lagneaux L, Najar M. The potential of mesenchymal stromal cells in immunotherapy. Immunotherapy. 2016;8:839–42.

    Article  CAS  PubMed  Google Scholar 

  12. Ankrum JA, Ong JF, Karp JM. Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotechnol. 2014;32:252–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Shi Y, Cao J, Wang Y. Rethinking regeneration: empowerment of stem cells by inflammation. Cell Death Differ. 2015;22:1891–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wang Y, Chen X, Cao W, Shi Y. Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol. 2014;15:1009–16.

    Article  CAS  PubMed  Google Scholar 

  15. Redondo-Castro E, Cunningham C, Miller J, Martuscelli L, Aoulad-Ali S, Rothwell NJ, et al. Interleukin-1 primes human mesenchymal stem cells towards an anti-inflammatory and pro-trophic phenotype in vitro. Stem Cell Res Ther. 2017;8:79.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Najar M, Raicevic G, Fayyad-Kazan H, Bron D, Toungouz M, Lagneaux L. Mesenchymal stromal cells and immunomodulation: a gathering of regulatory immune cells. Cytotherapy. 2016;18:160–71.

    Article  CAS  PubMed  Google Scholar 

  17. Najar M, Raicevic G, Crompot E, Fayyad-Kazan H, Bron D, Toungouz M, et al. The immunomodulatory potential of mesenchymal stromal cells: a story of a regulatory network. J Immunother Hagerstown Md 1997. 2016;39:45–59.

    CAS  Google Scholar 

  18. Caplan AI. Mesenchymal stem cells: time to change the name! Stem Cells Transl Med. 2017;6(6):1445–1451.

  19. Goldstein MG, Li Z. Heat-shock proteins in infection-mediated inflammation-induced tumorigenesis. J Hematol OncolJ Hematol Oncol. 2009;2:5.

    Article  CAS  Google Scholar 

  20. Hall SW, Cooke A. Autoimmunity and inflammation: murine models and translational studies. Mamm Genome Off J Int Mamm Genome Soc. 2011;22:377–89.

    Article  CAS  Google Scholar 

  21. Dinarello CA. Proinflammatory cytokines. Chest. 2000;118:503–8.

    Article  CAS  PubMed  Google Scholar 

  22. Mukaida N. [Inflammation and pro-inflammatory cytokine]. Nihon Rinsho Jpn J Clin Med. 1992;50:1724–9.

    CAS  Google Scholar 

  23. Hemeda H, Jakob M, Ludwig A-K, Giebel B, Lang S, Brandau S. Interferon-gamma and tumor necrosis factor-alpha differentially affect cytokine expression and migration properties of mesenchymal stem cells. Stem Cells Dev. 2010;19:693–706.

    Article  CAS  PubMed  Google Scholar 

  24. Barry FP, Murphy JM. Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol. 2004;36:568–84.

    Article  CAS  PubMed  Google Scholar 

  25. Crop MJ, Baan CC, Korevaar SS, Ijzermans JNM, Pescatori M, Stubbs AP, et al. Inflammatory conditions affect gene expression and function of human adipose tissue-derived mesenchymal stem cells. Clin Exp Immunol. 2010;162:474–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Prasanna SJ, Gopalakrishnan D, Shankar SR, Vasandan AB. Pro-inflammatory cytokines, IFNgamma and TNFalpha, influence immune properties of human bone marrow and Wharton jelly mesenchymal stem cells differentially. PloS One. 2010;5:e9016.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Haynesworth SE, Baber MA, Caplan AI. Cytokine expression by human marrow-derived mesenchymal progenitor cells in vitro: effects of dexamethasone and IL-1 alpha. J Cell Physiol. 1996;166:585–92.

    Article  CAS  PubMed  Google Scholar 

  28. Najar M, Raicevic G, Fayyad-Kazan H, Kazan HF, De Bruyn C, Bron D, et al. Immune-related antigens, surface molecules and regulatory factors in human-derived mesenchymal stromal cells: the expression and impact of inflammatory priming. Stem Cell Rev. 2012;8:1188–98.

    Article  CAS  PubMed  Google Scholar 

  29. Feghali CA, Wright TM. Cytokines in acute and chronic inflammation. Front Biosci J Virtual Libr. 1997;2:d12-26.

    Google Scholar 

  30. Medzhitov R, Horng T. Transcriptional control of the inflammatory response. Nat Rev Immunol. 2009;9:692–703.

    Article  CAS  PubMed  Google Scholar 

  31. Daxecker H, Raab M, Markovic S, Karimi A, Griesmacher A, Mueller MM. Endothelial adhesion molecule expression in an in vitro model of inflammation. Clin Chim Acta Int J Clin Chem. 2002;325:171–5.

    Article  CAS  Google Scholar 

  32. Hoogduijn MJ, Popp F, Verbeek R, Masoodi M, Nicolaou A, Baan C, et al. The immunomodulatory properties of mesenchymal stem cells and their use for immunotherapy. Int Immunopharmacol. 2010;10:1496–500.

    Article  CAS  PubMed  Google Scholar 

  33. Kyurkchiev D, Bochev I, Ivanova-Todorova E, Mourdjeva M, Oreshkova T, Belemezova K, et al. Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J Stem Cells. 2014;6:552–70.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Caplan AI. MSCs. The sentinel and safe-guards of injury. J Cell Physiol. 2016;231:1413–6.

    Article  CAS  PubMed  Google Scholar 

  35. Fu X, Chen Y, **e F-N, Dong P, Liu W, Cao Y, et al. Comparison of immunological characteristics of mesenchymal stem cells derived from human embryonic stem cells and bone marrow. Tissue Eng Part A. 2015;21:616–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chan WK, Lau AS-Y, Li JC-B, Law HK-W, Lau YL, Chan GC-F. MHC expression kinetics and immunogenicity of mesenchymal stromal cells after short-term IFN-gamma challenge. Exp Hematol. 2008;36:1545–55.

    Article  CAS  PubMed  Google Scholar 

  37. Chan JL, Tang KC, Patel AP, Bonilla LM, Pierobon N, Ponzio NM, et al. Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-gamma. Blood. 2006;107:4817–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Romieu-Mourez R, François M, Boivin M-N, Stagg J, Galipeau J. Regulation of MHC class II expression and antigen processing in murine and human mesenchymal stromal cells by IFN-gamma, TGF-beta, and cell density. J Immunol Baltim Md 1950. 2007;179:1549–58.

    CAS  Google Scholar 

  39. Stagg J, Pommey S, Eliopoulos N, Galipeau J. Interferon-gamma-stimulated marrow stromal cells: a new type of nonhematopoietic antigen-presenting cell. Blood. 2006;107:2570–7.

    Article  CAS  PubMed  Google Scholar 

  40. Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringdén O. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol. 2003;31:890–6.

    Article  PubMed  CAS  Google Scholar 

  41. Fasslrinner F, Wobus M, Duryagina R, Müller K, Stopp S, Wehner R, et al. Differential effects of mixed lymphocyte reaction supernatant on human mesenchymal stromal cells. Exp Hematol. 2012;40:934–44.

    Article  CAS  PubMed  Google Scholar 

  42. Polchert D, Sobinsky J, Douglas G, Kidd M, Moadsiri A, Reina E, et al. IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur J Immunol. 2008;38:1745–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Pourgholaminejad A, Aghdami N, Baharvand H, Moazzeni SM. The effect of pro-inflammatory cytokines on immunophenotype, differentiation capacity and immunomodulatory functions of human mesenchymal stem cells. Cytokine. 2016;85:51–60.

    Article  CAS  PubMed  Google Scholar 

  44. Kanematsu D, Kanemura Y. Cellular properties of mesenchymal cells derived from the decidua of human term placenta and their applications in regenerative medicine. In: De Bartolo L, Bader A, editors. Biomaterials for stem cell therapy. CRC Press. 2013; p. 228–248.

  45. Okolicsanyi RK, Camilleri ET, Oikari LE, Yu C, Cool SM, van Wijnen AJ, et al. Human mesenchymal stem cells retain multilineage differentiation capacity including neural marker expression after extended in vitro expansion. PLoS One. 2015;10(9): e0137255.

  46. Yeh S-P, Chang J-G, Lo W-J, Liaw Y-C, Lin C-L, Lee C-C, et al. Induction of CD45 expression on bone marrow-derived mesenchymal stem cells. Leukemia. 2006;20:894–6.

    Article  CAS  PubMed  Google Scholar 

  47. Garcia J, Wright K, Roberts S, Kuiper JH, Mangham C, Richardson J, et al. Characterisation of synovial fluid and infrapatellar fat pad derived mesenchymal stromal cells: the influence of tissue source and inflammatory stimulus. Sci Rep. 2016;6:24295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kronsteiner B, Wolbank S, Peterbauer A, Hackl C, Redl H, van Griensven M, et al. 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;20:2115–26.

    Article  CAS  PubMed  Google Scholar 

  49. Miettinen JA, Pietilä M, Salonen RJ, Ohlmeier S, Ylitalo K, Huikuri HV, et al. Tumor necrosis factor alpha promotes the expression of immunosuppressive proteins and enhances the cell growth in a human bone marrow-derived stem cell culture. Exp Cell Res. 2011;317:791–801.

    Article  CAS  PubMed  Google Scholar 

  50. Quaedackers ME, Baan CC, Weimar W, Hoogduijn MJ. Cell contact interaction between adipose-derived stromal cells and allo-activated T lymphocytes. Eur J Immunol. 2009;39:3436–46.

    Article  CAS  PubMed  Google Scholar 

  51. Kassem M, Abdallah BM. Human bone-marrow-derived mesenchymal stem cells: biological characteristics and potential role in therapy of degenerative diseases. Cell Tissue Res. 2008;331:157–63.

    Article  PubMed  Google Scholar 

  52. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science. 1997;276:71–4.

    Article  CAS  PubMed  Google Scholar 

  53. da Silva Meirelles L, Chagastelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci. 2006;119:2204–13.

    Article  PubMed  CAS  Google Scholar 

  54. Deshpande S, James AW, Blough J, Donneys A, Wang SC, Cederna PS, et al. Reconciling the effects of inflammatory cytokines on mesenchymal cell osteogenic differentiation. J Surg Res. 2013;185:278–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Lacey DC, Simmons PJ, Graves SE, Hamilton JA. Proinflammatory cytokines inhibit osteogenic differentiation from stem cells: implications for bone repair during inflammation. Osteoarthr Cartil. 2009;17:735–42.

    Article  CAS  PubMed  Google Scholar 

  56. Hosogane N, Huang Z, Rawlins BA, Liu X, Boachie-Adjei O, Boskey AL, et al. Stromal derived factor-1 regulates bone morphogenetic protein 2-induced osteogenic differentiation of primary mesenchymal stem cells. Int J Biochem Cell Biol. 2010;42:1132–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Wang M, Crisostomo PR, Herring C, Meldrum KK, Meldrum DR. Human progenitor cells from bone marrow or adipose tissue produce VEGF, HGF, and IGF-I in response to TNF by a p38 MAPK-dependent mechanism. Am J Physiol Regul Integr Comp Physiol. 2006;291:R880-884.

    Google Scholar 

  58. Standal T, Abildgaard N, Fagerli U-M, Stordal B, Hjertner O, Borset M, et al. HGF inhibits BMP-induced osteoblastogenesis: possible implications for the bone disease of multiple myeloma. Blood. 2007;109:3024–30.

    CAS  PubMed  Google Scholar 

  59. Hess K, Ushmorov A, Fiedler J, Brenner RE, Wirth T. TNFalpha promotes osteogenic differentiation of human mesenchymal stem cells by triggering the NF-kappaB signaling pathway. Bone. 2009;45:367–76.

    Article  CAS  PubMed  Google Scholar 

  60. Bastidas-Coral AP, Bakker AD, Zandieh-Doulabi B, Kleverlaan CJ, Bravenboer N, Forouzanfar T, et al. Cytokines TNF-α, IL-6, IL-17F, and IL-4 differentially affect osteogenic differentiation of human adipose stem cells. Stem Cells Int. 2016;2016:1318256.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Pricola KL, Kuhn NZ, Haleem-Smith H, Song Y, Tuan RS. Interleukin-6 maintains bone marrow-derived mesenchymal stem cell stemness by an ERK1/2-dependent mechanism. J Cell Biochem. 2009;108:577–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Mirantes C, Passegué E, Pietras EM. Pro-inflammatory cytokines: emerging players regulating HSC function in normal and diseased hematopoiesis. Exp Cell Res. 2014;329:248–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Heymann D, Rousselle AV. gp130 Cytokine family and bone cells. Cytokine. 2000;12:1455–68.

    Article  CAS  PubMed  Google Scholar 

  64. Rezaee F, Rellick SL, Piedimonte G, Akers SM, O’Leary HA, Martin K, et al. Neurotrophins regulate bone marrow stromal cell IL-6 expression through the MAPK pathway. PloS One. 2010;5:e9690.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Mukherjee A, Wilson EM, Rotwein P. Selective signaling by Akt2 promotes bone morphogenetic protein 2-mediated osteoblast differentiation. Mol Cell Biol. 2010;30:1018–27.

    Article  CAS  PubMed  Google Scholar 

  66. Greenblatt MB, Shim J-H, Zou W, Sitara D, Schweitzer M, Hu D, et al. The p38 MAPK pathway is essential for skeletogenesis and bone homeostasis in mice. J Clin Invest. 2010;120:2457–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Bunn RJ, Burke G, Connelly C, Li G, Marsh D. Inflammation–a double edged sword in high-energy fractures? In: Orthopaedic Proceedings, vol 87. 2015; p. 265–266.

  68. MacDougald OA, Mandrup S. Adipogenesis: forces that tip the scales. Trends Endocrinol Metab TEM. 2002;13:5–11.

    Article  CAS  PubMed  Google Scholar 

  69. Croes M, Öner FC, van Neerven D, Sabir E, Kruyt MC, Blokhuis TJ, et al. Proinflammatory T cells and IL-17 stimulate osteoblast differentiation. Bone. 2016;84:262–70.

    Article  CAS  PubMed  Google Scholar 

  70. Duijvestein M, Wildenberg ME, Welling MM, Hennink S, Molendijk I, van Zuylen VL, et al. Pretreatment with interferon-γ enhances the therapeutic activity of mesenchymal stromal cells in animal models of colitis. Stem Cells Dayt Ohio. 2011;29:1549–58.

    Article  CAS  Google Scholar 

  71. Duque G, Huang DC, Macoritto M, Rivas D, Yang XF, Ste-Marie LG, et al. Autocrine regulation of interferon gamma in mesenchymal stem cells plays a role in early osteoblastogenesis. Stem Cells Dayt Ohio. 2009;27:550–8.

    Article  CAS  Google Scholar 

  72. Vidal C, Bermeo S, Li W, Huang D, Kremer R, Duque G. Interferon gamma inhibits adipogenesis in vitro and prevents marrow fat infiltration in oophorectomized mice. Stem Cells Dayt Ohio. 2012;30:1042–8.

    Article  CAS  Google Scholar 

  73. Croitoru-Lamoury J, Lamoury FMJ, Caristo M, Suzuki K, Walker D, Takikawa O, et al. Interferon-γ regulates the proliferation and differentiation of mesenchymal stem cells via activation of indoleamine 2,3 dioxygenase (IDO). PloS One. 2011;6:e14698.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Vigo T, Procaccini C, Ferrara G, Baranzini S, Oksenberg JR, Matarese G, et al. IFNγ orchestrates mesenchymal stem cells plasticity through STAT1, STAT3 and mTOR pathways. J Allergy Clin Immunol. 2016.

  75. Sullivan CB, Porter RM, Evans CH, Ritter T, Shaw G, Barry F, et al. TNFα and IL-1β influence the differentiation and migration of murine MSCs independently of the NF-κB pathway. Stem Cell Res Ther. 2014;5:104.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Sonomoto K, Yamaoka K, Oshita K, Fukuyo S, Zhang X, Nakano K, et al. Interleukin-1β induces differentiation of human mesenchymal stem cells into osteoblasts via the Wnt-5a/receptor tyrosine kinase-like orphan receptor 2 pathway. Arthritis Rheum. 2012;64:3355–63.

    Article  CAS  PubMed  Google Scholar 

  77. Roux C, Pisani DF, Yahia HB, Djedaini M, Beranger GE, Chambard J-C, et al. Chondrogenic potential of stem cells derived from adipose tissue: a powerful pharmacological tool. Biochem Biophys Res Commun. 2013;440:786–91.

    Article  CAS  PubMed  Google Scholar 

  78. Majumdar MK, Wang E, Morris EA. BMP-2 and BMP-9 promotes chondrogenic differentiation of human multipotential mesenchymal cells and overcomes the inhibitory effect of IL-1. J Cell Physiol. 2001;189:275–84.

    Article  CAS  PubMed  Google Scholar 

  79. Felka T, Schäfer R, Schewe B, Benz K, Aicher WK. Hypoxia reduces the inhibitory effect of IL-1beta on chondrogenic differentiation of FCS-free expanded MSC. Osteoarthr Cartil. 2009;17:1368–76.

    Article  CAS  PubMed  Google Scholar 

  80. Cruz IBM da, Severo AL, Azzolin VF, Garcia LFM, Kuhn A, Lech O. Regenerative potential of the cartilaginous tissue in mesenchymal stem cells: update, limitations, and challenges. Rev Bras Ortop. 2017;52:2–10.

    Article  PubMed  Google Scholar 

  81. Wehling N, Palmer GD, Pilapil C, Liu F, Wells JW, Müller PE, et al. Interleukin-1beta and tumor necrosis factor alpha inhibit chondrogenesis by human mesenchymal stem cells through NF-kappaB-dependent pathways. Arthritis Rheum. 2009;60:801–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Boeuf S, Graf F, Fischer J, Moradi B, Little CB, Richter W. Regulation of aggrecanases from the ADAMTS family and aggrecan neoepitope formation during in vitro chondrogenesis of human mesenchymal stem cells. Eur Cell Mater. 2012;23:320–32.

    Article  CAS  PubMed  Google Scholar 

  83. Kondo M, Yamaoka K, Sonomoto K, Fukuyo S, Oshita K, Okada Y, et al. IL-17 inhibits chondrogenic differentiation of human mesenchymal stem cells. PloS One. 2013;8:e79463.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Jones E, Churchman SM, English A, Buch MH, Horner EA, Burgoyne CH, et al. Mesenchymal stem cells in rheumatoid synovium: enumeration and functional assessment in relation to synovial inflammation level. Ann Rheum Dis. 2010;69:450–7.

    Article  CAS  PubMed  Google Scholar 

  85. Pagani S, Borsari V, Veronesi F, Ferrari A, Cepollaro S, Torricelli P, et al. Increased chondrogenic potential of mesenchymal cells from adipose tissue versus bone marrow-derived cells in osteoarthritic in vitro models. J Cell Physiol. 2017;232:1478–88.

    Article  CAS  PubMed  Google Scholar 

  86. Ehninger A, Trumpp A. The bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move in. J Exp Med. 2011;208:421–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Méndez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, MacArthur BD, Lira SA, et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 2010;466:829–34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Schürch CM, Riether C, Ochsenbein AF. Cytotoxic CD8+ T cells stimulate hematopoietic progenitors by promoting cytokine release from bone marrow mesenchymal stromal cells. Cell Stem Cell. 2014;14:460–72.

    Article  PubMed  CAS  Google Scholar 

  89. Amouzegar A, Mittal SK, Sahu A, Sahu SK, Chauhan SK. Mesenchymal stem cells modulate differentiation of myeloid progenitor cells during inflammation. Ohio: Stem Cells Dayt; 2017.

    Google Scholar 

  90. Raefsky EL, Platanias LC, Zoumbos NC, Young NS. Studies of interferon as a regulator of hematopoietic cell proliferation. J Immunol Baltim Md 1950. 1985;135:2507–12.

    CAS  Google Scholar 

  91. Naveiras O, Nardi V, Wenzel PL, Hauschka PV, Fahey F, Daley GQ. Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature. 2009;460:259–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Goedhart M, Cornelissen A, Kuijk C, Geerman S, Pascutti F, Kleijer M, et al. Interferon-gamma impairs expansion and hematopoietic support of bone marrow mesenchymal stromal cells. Blood. 2016;128:3884–4.

    Google Scholar 

  93. Bigildeev AE, Zezina EA, Shipounova IN, Drize NJ. Interleukin-1 beta enhances human multipotent mesenchymal stromal cell proliferative potential and their ability to maintain hematopoietic precursor cells. Cytokine. 2015;71:246–54.

    Article  CAS  PubMed  Google Scholar 

  94. Zhao S, Wehner R, Bornhäuser M, Wassmuth R, Bachmann M, Schmitz M. Immunomodulatory properties of mesenchymal stromal cells and their therapeutic consequences for immune-mediated disorders. Stem Cells Dev. 2010;19:607–14.

    Article  CAS  PubMed  Google Scholar 

  95. Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008;8:726–36.

    Article  CAS  PubMed  Google Scholar 

  96. Bernardo ME, Fibbe WE. Mesenchymal stromal cells: sensors and switchers of inflammation. Cell Stem Cell. 2013;13:392–402.

    Article  CAS  PubMed  Google Scholar 

  97. 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 Rep. 2017.

  98. Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell. 2008;2:141–50.

    Article  CAS  PubMed  Google Scholar 

  99. Bai L, Lennon DP, Caplan AI, DeChant A, Hecker J, Kranso J, et al. Hepatocyte growth factor mediates mesenchymal stem cell-induced recovery in multiple sclerosis models. Nat Neurosci. 2012;15:862–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Raicevic G, Rouas R, Najar M, Stordeur P, Boufker HI, Bron D, et al. Inflammation modifies the pattern and the function of Toll-like receptors expressed by human mesenchymal stromal cells. Hum Immunol. 2010;71:235–44.

    Article  CAS  PubMed  Google Scholar 

  101. Raicevic G, Najar M, Stamatopoulos B, De Bruyn C, Meuleman N, Bron D, et al. The source of human mesenchymal stromal cells influences their TLR profile as well as their functional properties. Cell Immunol. 2011;270:207–16.

    Article  CAS  PubMed  Google Scholar 

  102. Klinker MW, Marklein RA, Lo Surdo JL, Wei C-H, Bauer SR. Morphological features of IFN-γ-stimulated mesenchymal stromal cells predict overall immunosuppressive capacity. Proc Natl Acad Sci USA. 2017.

  103. Guan Q, Ezzati P, Spicer V, Krokhin O, Wall D, Wilkins JA. Interferon γ induced compositional changes in human bone marrow derived mesenchymal stem/stromal cells. Clin. Proteomics. 2017;14:26.

  104. Ren G, Su J, Zhang L, Zhao X, Ling W, L’huillie A, et al. Species variation in the mechanisms of mesenchymal stem cell-mediated immunosuppression. Stem Cells Dayt Ohio. 2009;27:1954–62.

    Article  CAS  Google Scholar 

  105. Barrachina L, Remacha AR, Romero A, Vázquez FJ, Albareda J, Prades M, et al. Priming equine bone marrow-derived mesenchymal stem cells with proinflammatory cytokines: implications in immunomodulation-immunogenicity balance, cell viability, and differentiation potential. Stem Cells Dev. 2017;26:15–24.

    Article  CAS  PubMed  Google Scholar 

  106. Ryan JM, Barry F, Murphy JM, Mahon BP. Interferon-gamma does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells. Clin Exp Immunol. 2007;149:353–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Meisel R, Zibert A, Laryea M, Göbel U, Däubener W, Dilloo D. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood. 2004;103:4619–21.

    Article  CAS  PubMed  Google Scholar 

  108. Krampera M, Cosmi L, Angeli R, Pasini A, Liotta F, Andreini A, et al. Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells Dayt Ohio. 2006;24:386–98.

    Article  CAS  Google Scholar 

  109. DelaRosa O, Lombardo E, Beraza A, Mancheño-Corvo P, Ramirez C, Menta R, et al. Requirement of IFN-gamma-mediated indoleamine 2,3-dioxygenase expression in the modulation of lymphocyte proliferation by human adipose-derived stem cells. Tissue Eng Part A. 2009;15:2795–806.

    Article  CAS  PubMed  Google Scholar 

  110. Cuerquis J, Romieu-Mourez R, François M, Routy J-P, Young YK, Zhao J, 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.

    Article  CAS  PubMed  Google Scholar 

  111. Fechter K, Dorronsoro A, Jakobsson E, Ferrin I, Lang V, Sepulveda P, et al. IFNγ regulates activated Vδ2 + T Cells through a feedback mechanism mediated by mesenchymal stem cells. PloS One. 2017;12:e0169362.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Petinati NA, Kapranov NM, Bigil’deev AE, Popova MD, Davydova YO, Gal’tseva IV, et al. Changing the properties of multipotent mesenchymal stromal cells by IFNγ administration. Bull Exp Biol Med. 2017;163:230–4.

    Article  CAS  PubMed  Google Scholar 

  113. Zimmermann JA, Hettiaratchi MH, McDevitt TC. Enhanced immunosuppression of T cells by sustained presentation of bioactive interferon-γ within three-dimensional mesenchymal stem cell constructs. Stem Cells Transl Med. 2017;6:223–37.

    Article  CAS  PubMed  Google Scholar 

  114. Chinnadurai R, Rajan D, Ng S, McCullough K, Arafat D, Waller EK, et al. Immune dysfunctionality of replicative senescent mesenchymal stromal cells is corrected by IFNγ priming. Blood Adv. 2017;1:628–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Gieseke F, Schütt B, Viebahn S, Koscielniak E, Friedrich W, Handgretinger R, et al. Human multipotent mesenchymal stromal cells inhibit proliferation of PBMCs independently of IFNgammaR1 signaling and IDO expression. Blood. 2007;110:2197–200.

    Article  CAS  PubMed  Google Scholar 

  116. Chinnadurai R, Copland IB, Patel SR, Galipeau J. IDO-independent suppression of T cell effector function by IFN-γ-licensed human mesenchymal stromal cells. J Immunol Baltim Md 1950. 2014;192:1491–501.

    CAS  Google Scholar 

  117. English K, Barry FP, Field-Corbett CP, Mahon BP. IFN-gamma and TNF-alpha differentially regulate immunomodulation by murine mesenchymal stem cells. Immunol Lett. 2007;110:91–100.

    Article  CAS  PubMed  Google Scholar 

  118. Sheng H, Wang Y, ** Y, Zhang Q, Zhang Y, Wang L, et al. A critical role of IFNgamma in priming MSC-mediated suppression of T cell proliferation through up-regulation of B7-H1. Cell Res. 2008;18:846–57.

    Article  CAS  PubMed  Google Scholar 

  119. Chen K, Wang D, Du WT, Han Z-B, Ren H, Chi Y, et al. Human umbilical cord mesenchymal stem cells hUC-MSCs exert immunosuppressive activities through a PGE2-dependent mechanism. Clin Immunol Orlando Fla. 2010;135:448–58.

    Article  CAS  Google Scholar 

  120. Groh ME, Maitra B, Szekely E, Koç ON. Human mesenchymal stem cells require monocyte-mediated activation to suppress alloreactive T cells. Exp Hematol. 2005;33:928–34.

    Article  CAS  PubMed  Google Scholar 

  121. Prockop DJ, Oh JY. Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. Mol Ther J Am Soc Gene Ther. 2012;20:14–20.

    Article  CAS  Google Scholar 

  122. Minas K, Liversidge J. Is the CD200/CD200 receptor interaction more than just a myeloid cell inhibitory signal? Crit Rev Immunol. 2006;26:213–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Ren G, Zhao X, Zhang L, Zhang J, L’Huillier A, Ling W, et al. Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression. J Immunol Baltim Md 1950. 2010;184:2321–8.

    CAS  Google Scholar 

  124. Pontikoglou C, Langonné A, Ba MA, Varin A, Rosset P, Charbord P, et al. CD200 expression in human cultured bone marrow mesenchymal stem cells is induced by pro-osteogenic and pro-inflammatory cues. J Cell Mol Med. 2016;20:655–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Najar M, Raicevic G, Jebbawi F, De Bruyn C, Meuleman N, Bron D, et al. Characterization and functionality of the CD200–CD200R system during mesenchymal stromal cell interactions with T-lymphocytes. Immunol Lett. 2012;146:50–6.

    Article  CAS  PubMed  Google Scholar 

  126. Naji A, Suganuma N, Espagnolle N, Yagyu K-I, Baba N, Sensebé L, et al. Rationale for determining the functional potency of mesenchymal stem cells in preventing regulated cell death for therapeutic use. Stem Cells Transl Med. 2017;6:713–9.

    Article  CAS  PubMed  Google Scholar 

  127. Ma S, **e N, Li W, Yuan B, Shi Y, Wang Y. Immunobiology of mesenchymal stem cells. Cell Death Differ. 2014;21:216–25.

    Article  CAS  PubMed  Google Scholar 

  128. Kim N, Cho S-G. Overcoming immunoregulatory plasticity of mesenchymal stem cells for accelerated clinical applications. Int J Hematol. 2016;103:129–37.

    Article  CAS  PubMed  Google Scholar 

  129. Kusuma GD, Carthew J, Lim R, Frith JE. Effect of the microenvironment on mesenchymal stem cell paracrine signaling: opportunities to engineer the therapeutic effect. Stem Cells Dev. 2017;26:617–31.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Mehdi Najar and Mohammad Krayem have equally contributed.

Authors and Affiliations

  1. Laboratory of Clinical Cell Therapy, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Campus Erasme, Brussels, Belgium

    Mehdi Najar, Gordana Raicevic & Laurence Lagneaux

  2. Laboratory of Oncology and Experimental Surgery, Institut Jules Bordet, Université Libre de Bruxelles, 1 rue Heger-Bordet, 1000, Brussels, Belgium

    Mohammad Krayem

  3. Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, 121, Boulevard de Waterloo, 1000, Bruxelles, Belgium

    Makram Merimi, Arsène Burny, Nathalie Meuleman & Dominique Bron

Authors
  1. Mehdi Najar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammad Krayem
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Makram Merimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Arsène Burny
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nathalie Meuleman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dominique Bron
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gordana Raicevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Laurence Lagneaux
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohammad Krayem.

Ethics declarations

Conflict of interest

The authors declare no potential conflicts of interest.

Additional information

Communicated by John Di Battista.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Najar, M., Krayem, M., Merimi, M. et al. Insights into inflammatory priming of mesenchymal stromal cells: functional biological impacts. Inflamm. Res. 67, 467–477 (2018). https://doi.org/10.1007/s00011-018-1131-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-018-1131-1

Keywords

Search

Navigation