Skip to main content
SpringerLink
Log in

Immunoregulatory Functions of Mesenchymal Stromal Cells

  • Chapter
  • First Online:
Adult and Embryonic Stem Cells

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

  • 1317 Accesses

Abstract

In vitro and in vivo studies have demonstrated that mesenchymal stem cells (MSCs) are not immunogenic and do not have immunomodulatory effects. MSCs do not express class II antigens, FAS ligand, or co-stimulator molecules (CD80, CD86, CD40, CD40L). They have low expression of primary human leukocyte antigens (HLA-I). In vitro, MSCs in bone, cartilage, muscle, or fat differentiate in the case of HLA-I expression but do not express HLA-II antigens. However, the immunogenic effects of in vivo differentiated MSCs are controversial. MSCs suppress naive T lymphocytes, memory T lymphocytes, effector T lymphocytes, B lymphocytes, and natural killer (NK) cell functions. They are ineffective against the natural immune response of T lymphocytes. In the presence of antigen-presenting cells or antibodies, the addition of MSCs to a culture medium that includes HLA mismatch lymphocytes prevents T-lymphocyte stimulation. MSCs increase with B-lymphocyte viability in vitro and suppress interleukin-2 (IL-2)-related NK cell proliferation and the effector functions of NK cells. MSCs partially reduce the expression of major histocompatibility complex II and CD40 and CD86 co-stimulatory molecules from mature dendritic cells (DCs) by secreting a high rate of IL-6 and vascular endothelial growth factor and thus suppress DC-mediated T-lymphocyte proliferation.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105:1815–1822

    Article  PubMed  CAS  Google Scholar 

  • Bartholomew A, Sturgeon C, Siatskas M et al (2002) Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 30:42–48

    Article  PubMed  Google Scholar 

  • Bertrand FE, Eckfeldt CE, Fink JR, Lysholm AS, Pribyl JA, Shah N, LeBien TW (2000) Microenvironmental influences on human B cell development. Immunol Rev 175:175–186

    Article  PubMed  CAS  Google Scholar 

  • Beyth S, Borovsky Z, Mevorach D et al (2005) Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T cell unresponsiveness. Blood 105:2214–2219

    Article  PubMed  CAS  Google Scholar 

  • Chan JL, Tang KC, Patel AP et al (2006) Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-gamma. Blood 107:4817–4824

    Article  PubMed  CAS  Google Scholar 

  • Corcione A, Benvenuto F, Ferretti E et al (2006) Human mesenchymal stem cells modulate B cell functions. Blood 107:367–372

    Article  PubMed  CAS  Google Scholar 

  • Delorme B, Charbord P (2007) Culture and characterization of human bone marrow mesenchymal stem cells. Methods Mol Med 140:67–81

    Article  PubMed  CAS  Google Scholar 

  • Deng W, Han Q, Liao L et al (2005) Effects of allogeneic bone marrow-derived mesenchymal stem cells on T and B lymphocytes from BXSB mice. DNA Cell Biol 24:458–463

    Article  PubMed  CAS  Google Scholar 

  • Di Nicola M, Carlo-Stella C, Magni M et al (2002) Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99:3838–3843

    Article  PubMed  CAS  Google Scholar 

  • Eliopoulos N, Stagg J, Lejeune L, Pommey S, Galipeau J (2005) Allogeneic marrow stromal cells are immune rejected by MHC class I- and class II-mismatched recipient mice. Blood 106: 4057–4065

    Article  PubMed  CAS  Google Scholar 

  • Fibbe WE, Nauta AJ, Roelofs H (2007) Modulation of immune responses by mesenchymal stem cells. Ann N Y Acad Sci 1106:272–278

    Article  PubMed  CAS  Google Scholar 

  • Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP (1968) Heterotopic of bone marrow: analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 6: 230–247

    Article  PubMed  CAS  Google Scholar 

  • Glennie S, Soeiro I, Dyson PJ, Lam EW, Dazzi F (2005) Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood 105:2821–2827

    Article  PubMed  CAS  Google Scholar 

  • Horwitz E, Le Blanc K, Dominici M et al (2005) Clarification of the nomenclature for MSC: the International Society for Cellular Therapy position statement. Cytotherapy 7:393–395

    Article  PubMed  CAS  Google Scholar 

  • Huang W, La Russa V, Alzoubi A, Schwarzenberger P (2006) Interleukin-17A: a T-cell derived growth factor for murine and human mesenchymal stem cells. Stem Cells 24:1512–1518

    Article  PubMed  CAS  Google Scholar 

  • Jiang XX, Zhang Y, Liu B et al (2005) Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood 105:4120–4126

    Article  PubMed  CAS  Google Scholar 

  • Jung YJ, Ju SY, Yoo ES et al (2007) MSC-DC interactions: MSC inhibit maturation and migration of BM-derived DC. Cytotherapy 9(5):451–458

    Article  PubMed  CAS  Google Scholar 

  • Kim DH, Yoo KH, Choi KS et al (2005) Gene expression profile of cytokine and growth factor during differentiation of bone marrow-derived mesenchymal stem cell. Cytokine 31:119–126

    Article  PubMed  CAS  Google Scholar 

  • Klyushnenkova E, Mosca JD, Zernetkina V et al (2005) T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression. J Biomed Sci 12:47–57

    Article  PubMed  CAS  Google Scholar 

  • Koc ON, Day J, Nieder M et al (2002) Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH). Bone Marrow Transplant 30:215–222

    Article  PubMed  CAS  Google Scholar 

  • Krampera M, Glennie S, Dyson J et al (2003) Bone marrow mesenchymal stem cells inhibit the response of naïve and memory antigen-specific T cells to their cognate peptide. Blood 101:3722–3729

    Article  PubMed  CAS  Google Scholar 

  • Krampera M, Cosmi L, Angeli R et al (2006) Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells 24:386–398

    Article  PubMed  CAS  Google Scholar 

  • Le Blanc K, Ringden O (2005) Immunobiology of human mesenchymal stem cells and future use in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 11:321–334

    Article  PubMed  CAS  Google Scholar 

  • Le Blanc K, Ringden O (2006) Mesenchymal stem cells: properties and role in clinical bone marrow transplantation. Curr Opin Immunol 18:586–591

    Article  PubMed  CAS  Google Scholar 

  • Le Blanc K, Tammik L, Sundberg B, Haynesworth SE, Ringden O (2003a) Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol 57:11–20

    Article  PubMed  CAS  Google Scholar 

  • Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringden O (2003b) HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 10:890–896

    Article  Google Scholar 

  • Le Blanc K, Tammik L, Zetterberg E, Ringden O (2003c) HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 31:890–896

    Article  PubMed  CAS  Google Scholar 

  • Locatelli F, Maccario R, Frassoni F (2007) Mesenchymal stromal cells, from indifferent spectators to principal actors: are we going to witness a revolution in the scenario of allograft and immune-mediated disorders? Haematologica 92:872–877

    Article  PubMed  Google Scholar 

  • Maccario R, Podestà M, Moretta A et al (2005a) Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T-cell subsets expressing a regulatory/suppressive phenotype. Haematologica 90:516–525

    PubMed  CAS  Google Scholar 

  • Maccario R, Moretta A, Cometa A et al (2005b) Human mesenchymal stem cells and cyclosporin-A exert a synergistic suppressive effect on in vitro activation of alloantigen-specific cytotoxic lymphocytes. Biol Blood Marrow Transplant 11:1031–1032

    Article  PubMed  Google Scholar 

  • Majumdar MK, Keane-Moore M, Buyaner D et al (2003) Characterization and functionality of cell surface molecules on human mesenchymal stem cells. J Biomed Sci 10:228–241

    Article  PubMed  CAS  Google Scholar 

  • Meisel R, Zibert A, Laryea M, Gobel U, Daubener W, Dilloo D (2004) Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3 dioxygenase-mediated tryptophan degradation. Blood 103:4619–4621

    Article  PubMed  CAS  Google Scholar 

  • Moretta L, Moretta A (2004) Unravelling natural killer cell function: triggering and inhibitory human NK receptors. EMBO J 23:255–259

    Article  PubMed  CAS  Google Scholar 

  • Moretta A, Bottino C, Vitale M et al (2001) Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 19:197–223

    Article  PubMed  CAS  Google Scholar 

  • Nauta AJ, Kruisselbrink AB, Lurvink E, Willemze R, Fibbe WE (2006a) Mesenchymal stem cells inhibit generation and function of both CD34+-derived and monocyte-derived dendritic cells. J Immunol 177:2080–2087

    PubMed  CAS  Google Scholar 

  • Nauta AJ, Westerhuis G, Kruisselbrink AB, Lurvink EG, Willemze R, Fibbe WE (2006b) Donor-derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a non-myeloablative setting. Blood 108:2114–2120

    Article  PubMed  CAS  Google Scholar 

  • Nevruz O, Avcu F, Ural AU et al (2007) Immunosuppressive effects of multipotent mesenchymal stromal cells on graft-versus-host disease in rats following allogeneic bone marrow transplantation. Blood 110(11): Abstr. 3248

    Google Scholar 

  • Poggi A, Prevosto C, Massaro AM et al (2005) Interaction between human NK cells and bone marrow stromal cells induces NK cell triggering: role of NKp30 and NKG2D receptors. J Immunol 175:6352–6360

    PubMed  CAS  Google Scholar 

  • Potian JA, Aviv H, Ponzio NM, Harrison JS, Rameshwar P (2003) Veto-like activity of mesenchymal stem cells: functional discrimination between cellular responses to alloantigens and recall antigens. J Immunol 171:3426–3434

    PubMed  CAS  Google Scholar 

  • Ramasamy R, Fazekasova H, Lam EW, Soeiro I, Lombardi G, Dazzi F (2007) Mesenchymal stem cells inhibit dendritic cell differentiation and function by preventing entry into the cell cycle. Transplantation 83(1):71–76

    Article  PubMed  Google Scholar 

  • Renner P, Eggenhofer E, Rosenauer A et al (2009) Mesenchymal stem cells require a sufficient, ongoing immune response to exert their immunosuppressive function. Transplant Proc 41(6):2607–2611

    Article  PubMed  CAS  Google Scholar 

  • Rutella S, Danese S, Leone G (2006) Tolerogenic dendritic cells: cytokine modulation comes of age. Blood 108:1435–1440

    Article  PubMed  CAS  Google Scholar 

  • Salem HK, Thıemermann C (2010) Mesenchymal stromal cells: current understanding and clinical status. Stem Cells 28:585–596

    PubMed  CAS  Google Scholar 

  • Selmani Z, Naji A, Gaiffe E et al (2009) HLA-G is a crucial immunosuppressive molecule secreted by adult human mesenchymal stem cells. Transplantation 87(9 Suppl):S62–S66

    Article  PubMed  CAS  Google Scholar 

  • Siegel G, Schäfer R, Dazzi F (2009) The immunosuppressive properties of mesenchymal stem cells. Transplantation 87(9 Suppl):S45–S49

    Article  PubMed  Google Scholar 

  • Son BR, Marquez-Curtis LA, Kucia M et al (2006) Migration of bone marrow and cord blood mesenchymal stem cells in vitro is regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor-c-met axes and involves matrix metalloproteinases. Stem Cells 24:1254–1264

    Article  PubMed  CAS  Google Scholar 

  • Sotiropoulou PA, Perez SA, Gritzapis AP et al (2006) Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells 24:74–85

    Article  PubMed  Google Scholar 

  • Spaggiari GM, Capobianco A, Becchetti S, Mingari MC, Moretta L (2006) 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 107:1484–1490

    Article  PubMed  CAS  Google Scholar 

  • Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, Moretta L (2008) Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood 111(3):1327–1333

    Article  PubMed  CAS  Google Scholar 

  • Strobl H, Knapp W (1999) TGF-β1 regulation of dendritic cells. Microbes Infect 1:1283–1291

    Article  PubMed  CAS  Google Scholar 

  • Tse WT, Pendleton JD, Beyer WM, Egalka MC, Guinan EC (2003) Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 75:389–397

    Article  PubMed  CAS  Google Scholar 

  • Uccelli A, Moretta L, Pistoia V (2006) Immunoregulatory function of mesenchymal stem cells. Eur J Immunol 36(10):2566–2573

    Article  PubMed  CAS  Google Scholar 

  • Uccelli A, Pistoia V, Moretta L (2007) Mesenchymal stem cells: a new strategy for immunosuppression? Trends Immunol 28:219–226

    Article  PubMed  CAS  Google Scholar 

  • Valtieri M, Sorrentino A (2008) The mesenchymal stromal cell contribution to homeostasis. J Cell Physiol 217(2):296–300

    Article  PubMed  CAS  Google Scholar 

  • Wilson A, Trumpp A (2006) Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol 6(2):93–106

    Article  PubMed  CAS  Google Scholar 

  • Zhang W, Ge W, Li C et al (2004) Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells. Stem Cells Dev 13:263–271

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology and Research Center, Gulhane Medical Faculty, Tevfik Saglam Street, 06018, Etlik/Ankara, Turkiye

    Ferit Avcu M.D.

Authors
  1. Ferit Avcu M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ferit Avcu M.D. .

Editor information

Editors and Affiliations

  1. Smyth Rd 501, Ottawa, K1H 8L6, Canada

    Kursad Turksen

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Avcu, F. (2012). Immunoregulatory Functions of Mesenchymal Stromal Cells. In: Turksen, K. (eds) Adult and Embryonic Stem Cells. Stem Cell Biology and Regenerative Medicine. Humana Press. https://doi.org/10.1007/978-1-61779-630-2_5

Download citation

Publish with us

Policies and ethics

Search

Navigation