Skip to main content
SpringerLink
Log in

Therapeutic Potential of Mesenchymal Stem Cells in Immune-Mediated Diseases

  • Chapter
  • First Online:
Stem Cells

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1201))

Abstract

Mesenchymal stem cells (MSCs) are multipotent cells that can self-renew and differentiate into cells of all germ layers. MSCs can be easily attracted to the site of tissue insult with high levels of inflammatory mediators. The general ability of MSCs to migrate at the sites of tissue injury suggested an innate ability for these cells to be involved in baseline tissue repair. The bone marrow is one of the primary sources of MSCs, though they can be ubiquitous. An attractive property of MSCs for clinical application is their ability to cross allogeneic barrier. However, alone, MSCs are not immune suppressive cells. Rather, they can be licensed by the tissue microenvironment to become immune suppressor cells. Immune suppressor functions of MSCs include those that blunt cytotoxicity of natural killer cells, suppression of T-cell proliferation, and “veto” function. MSCs, as third-party cells, suppress the immune response that generally recapitulates graft-versus-host disease (GvHD) responses. Based on the plastic functions of MSCs, these cells have dominated the field of cell-based therapies, such as anti-inflammatory and drug delivery. Here, we focus on the potential use of MSC for immunological disorders such as Crohn’s disease and GvHD.

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 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
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

  1. Ullah I, Subbarao RB, Rho GJ (2015) Human mesenchymal stem cells – current trends and future prospective. Biosci Rep 35:e00191

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Kassem M, Kristiansen M, Abdallah BM (2004) Mesenchymal stem cells: cell biology and potential use in therapy. Basic Clin Pharmacol Toxicol 95(5):209–214

    Article  CAS  PubMed  Google Scholar 

  3. De Miguel MP, Fuentes-Julian S, Blazquez-Martinez A, Pascual CY, Aller MA, Arias J, Arnalich-Montiel F (2012) Immunosuppressive properties of mesenchymal stem cells: advances and applications. Curr Mol Med 12(5):574–591

    Article  PubMed  Google Scholar 

  4. Hoogduijn MJ, Popp F, Verbeek R, Masoodi M, Nicolaou A, Baan C, Dahlke MH (2010) The immunomodulatory properties of mesenchymal stem cells and their use for immunotherapy. Int Immunopharmacol 10(12):1496–1500

    Article  CAS  PubMed  Google Scholar 

  5. Pontikoglou C, Deschaseaux F, Sensebe L, Papadaki HA (2011) Bone marrow mesenchymal stem cells: biological properties and their role in hematopoiesis and hematopoietic stem cell transplantation. Stem Cell Rev 7(3):569–589

    Article  Google Scholar 

  6. Mendez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, Macarthur BD, Lira SA, Scadden DT, Ma’ayan A, Enikolopov GN, Frenette PS (2010) Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466(7308):829–834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ehninger A, Trumpp A (2011) The bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move in. J Exp Med 208(3):421–428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Mahmoudifar N, Doran PM (2015) Mesenchymal stem cells derived from human adipose tissue. Methods Mol Biol 1340:53–64

    Article  CAS  PubMed  Google Scholar 

  9. Hoogduijn MJ, Betjes MG, Baan CC (2014) Mesenchymal stromal cells for organ transplantation: different sources and unique characteristics? Curr Opin Organ Transplant 19(1):41–46

    Article  CAS  PubMed  Google Scholar 

  10. Lv FJ, Tuan RS, Cheung KM, Leung VY (2014) The surface markers and identity of human mesenchymal stem cells. Stem Cells 32(6):1408–1419

    Article  CAS  PubMed  Google Scholar 

  11. Chan JL, Tang KC, Patel AP, Bonilla LM, Pierobon N, Ponzio NM, Rameshwar P (2006) Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-gamma. Blood 107(12):4817–4824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wei X, Yang X, Han ZP, Qu FF, Shao L, Shi YF (2013) Mesenchymal stem cells: a new trend for cell therapy. Acta Pharmacol Sin 34(6):747–754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Petri RM, Hackel A, Hahnel K, Dumitru CA, Bruderek K, Flohe SB, Paschen A, Lang S, Brandau S (2017) Activated tissue-resident mesenchymal stromal cells regulate natural killer cell immune and tissue-regenerative function. Stem Cell Reports 9(3):985–998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Choi H, Lee RH, Bazhanov N, Oh JY, Prockop DJ (2011) Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan-induced mouse peritonitis by decreasing TLR2/NF-kappaB signaling in resident macrophages. Blood 118(2):330–338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sordi V (2009) Mesenchymal stem cell homing capacity. Transplantation 87:S42–S45

    Article  PubMed  Google Scholar 

  16. Sundin M, Barrett AJ, Ringden O, Uzunel M, Lonnies H, Dackland AL, Christensson B, Blanc KL (2009) HSCT recipients have specific tolerance to MSC but not to the MSC donor. J Immunother 32(7):755–764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Krueger TEG, Thorek DLJ, Denmeade SR, Isaacs JT, Brennen WN (2018) Concise review: mesenchymal stem cell-based drug delivery: the good, the bad, the ugly, and the promise. Stem Cells Transl Med 7(9):651–663

    Article  PubMed  PubMed Central  Google Scholar 

  18. Ankrum JA, Ong JF, Karp JM (2014) Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotechnol 32(3):252–260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. 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(5):321–334

    Article  PubMed  CAS  Google Scholar 

  20. Le Blanc K, Tammik L, Sundberg B, Haynesworth SE, Ringden O (2003) Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol 57(1):11–20

    Article  PubMed  Google Scholar 

  21. Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105(4):1815–1822

    Article  CAS  PubMed  Google Scholar 

  22. Patel SA, Meyer JR, Greco SJ, Corcoran KE, Bryan M, Rameshwar P (2010) Mesenchymal stem cells protect breast cancer cells through regulatory T cells: role of mesenchymal stem cell-derived TGF-beta. J Immunol 184(10):5885–5894

    Article  CAS  PubMed  Google Scholar 

  23. Gieseke F, Bohringer J, Bussolari R, Dominici M, Handgretinger R, Muller I (2010) Human multipotent mesenchymal stromal cells use galectin-1 to inhibit immune effector cells. Blood 116(19):3770–3779

    Article  CAS  PubMed  Google Scholar 

  24. Ling W, Zhang J, Yuan Z, Ren G, Zhang L, Chen X, Rabson AB, Roberts AI, Wang Y, Shi Y (2014) Mesenchymal stem cells use IDO to regulate immunity in tumor microenvironment. Cancer Res 74(5):1576–1587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Yang SH, Park MJ, Yoon IH, Kim SY, Hong SH, Shin JY, Nam HY, Kim YH, Kim B, Park CG (2009) Soluble mediators from mesenchymal stem cells suppress T cell proliferation by inducing IL-10. Exp Mol Med 41(5):315–324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhai L, Spranger S, Binder DC, Gritsina G, Lauing KL, Giles FJ, Wainwright DA (2015) Molecular pathways: targeting IDO1 and other tryptophan dioxygenases for cancer immunotherapy. Clin Cancer Res 21(24):5427–5433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM (2002) Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99(10):3838–3843

    Article  PubMed  Google Scholar 

  28. Chabannes D, Hill M, Merieau E, Rossignol J, Brion R, Soulillou JP, Anegon I, Cuturi MC (2007) A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells. Blood 110(10):3691–3694

    Article  CAS  PubMed  Google Scholar 

  29. Su J, Chen X, Huang Y, Li W, Li J, Cao K, Cao G, Zhang L, Li F, Roberts AI, Kang H, Yu P, Ren G, Ji W, Wang Y, Shi Y (2014) Phylogenetic distinction of iNOS and IDO function in mesenchymal stem cell-mediated immunosuppression in mammalian species. Cell Death Differ 21(3):388–396

    Article  CAS  PubMed  Google Scholar 

  30. Akiyama K, Chen C, Wang D, Xu X, Qu C, Yamaza T, Cai T, Chen W, Sun L, Shi S (2012) Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis. Cell Stem Cell 10(5):544–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lee HK, Kim HS, Kim JS, Kim YG, Park KH, Lee JH, Kim KH, Chang IY, Bae SC, Kim Y, Hong JT, Kehrl JH, Han SB (2017) CCL2 deficient mesenchymal stem cells fail to establish long-lasting contact with T cells and no longer ameliorate lupus symptoms. Sci Rep 7:41258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ren G, Zhao X, Zhang L, Zhang J, L’Huillier A, Ling W, Roberts AI, Le AD, Shi S, Shao C, Shi Y (2010) Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression. J Immunol 184(5):2321–2328

    Article  CAS  PubMed  Google Scholar 

  33. Maccario R, Podesta M, Moretta A, Cometa A, Comoli P, Montagna D, Daudt L, Ibatici A, Piaggio G, Pozzi S, Frassoni F, Locatelli F (2005) 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(4):516–525

    CAS  PubMed  Google Scholar 

  34. Ramasamy R, Tong CK, Seow HF, Vidyadaran S, Dazzi F (2008) The immunosuppressive effects of human bone marrow-derived mesenchymal stem cells target T cell proliferation but not its effector function. Cell Immunol 251(2):131–136

    Article  CAS  PubMed  Google Scholar 

  35. Bai L, Lennon DP, Eaton V, Maier K, Caplan AI, Miller SD, Miller RH (2009) Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis. Glia 57(11):1192–1203

    Article  PubMed  PubMed Central  Google Scholar 

  36. Choi EW, Lee M, Song JW, Shin IS, Kim SJ (2016) Mesenchymal stem cell transplantation can restore lupus disease-associated miRNA expression and Th1/Th2 ratios in a murine model of SLE. Sci Rep 6:38237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Luz-Crawford P, Kurte M, Bravo-Alegria J, Contreras R, Nova-Lamperti E, Tejedor G, Noel D, Jorgensen C, Figueroa F, Djouad F, Carrion F (2013) Mesenchymal stem cells generate a CD4+CD25+Foxp3+ regulatory T cell population during the differentiation process of Th1 and Th17 cells. Stem Cell Res Ther 4(3):65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Cho KS, Park HK, Park HY, Jung JS, Jeon SG, Kim YK, Roh HJ (2009) IFATS collection: immunomodulatory effects of adipose tissue-derived stem cells in an allergic rhinitis mouse model. Stem Cells 27(1):259–265

    Article  CAS  PubMed  Google Scholar 

  39. Kavanagh H, Mahon BP (2011) Allogeneic mesenchymal stem cells prevent allergic airway inflammation by inducing murine regulatory T cells. Allergy 66(4):523–531

    Article  CAS  PubMed  Google Scholar 

  40. Zhou H, Guo M, Bian C, Sun Z, Yang Z, Zeng Y, Ai H, Zhao RC (2010) Efficacy of bone marrow-derived mesenchymal stem cells in the treatment of sclerodermatous chronic graft-versus-host disease: clinical report. Biol Blood Marrow Transplant 16(3):403–412

    Article  CAS  PubMed  Google Scholar 

  41. Sakaguchi S, Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T (2009) Regulatory T cells: how do they suppress immune responses? Int Immunol 21(10):1105–1111

    Article  CAS  PubMed  Google Scholar 

  42. Melief SM, Schrama E, Brugman MH, Tiemessen MM, Hoogduijn MJ, Fibbe WE, Roelofs H (2013) Multipotent stromal cells induce human regulatory T cells through a novel pathway involving skewing of monocytes toward anti-inflammatory macrophages. Stem Cells 31(9):1980–1991

    Article  CAS  PubMed  Google Scholar 

  43. English K, Ryan JM, Tobin L, Murphy MJ, Barry FP, Mahon BP (2009) Cell contact, prostaglandin E(2) and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4+CD25(high) forkhead box P3+ regulatory T cells. Clin Exp Immunol 156(1):149–160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Selmani Z, Naji A, Zidi I, Favier B, Gaiffe E, Obert L, Borg C, Saas P, Tiberghien P, Rouas-Freiss N, Carosella ED, Deschaseaux F (2008) 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 26(1):212–222

    Article  CAS  PubMed  Google Scholar 

  45. Zacchigna S, Martinelli V, Moimas S, Colliva A, Anzini M, Nordio A, Costa A, Rehman M, Vodret S, Pierro C, Colussi G, Zentilin L, Gutierrez MI, Dirkx E, Long C, Sinagra G, Klatzmann D, Giacca M (2018) Paracrine effect of regulatory T cells promotes cardiomyocyte proliferation during pregnancy and after myocardial infarction. Nat Commun 9(1):2432

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Burzyn D, Kuswanto W, Kolodin D, Shadrach JL, Cerletti M, Jang Y, Sefik E, Tan TG, Wagers AJ, Benoist C, Mathis D (2013) A special population of regulatory T cells potentiates muscle repair. Cell 155(6):1282–1295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Arpaia N, Green JA, Moltedo B, Arvey A, Hemmers S, Yuan S, Treuting PM, Rudensky AY (2015) A distinct function of regulatory T cells in tissue protection. Cell 162(5):1078–1089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Dombrowski Y, O’Hagan T, Dittmer M, Penalva R, Mayoral SR, Bankhead P, Fleville S, Eleftheriadis G, Zhao C, Naughton M, Hassan R, Moffat J, Falconer J, Boyd A, Hamilton P, Allen IV, Kissenpfennig A, Moynagh PN, Evergren E, Perbal B, Williams AC, Ingram RJ, Chan JR, Franklin RJM, Fitzgerald DC (2017) Regulatory T cells promote myelin regeneration in the central nervous system. Nat Neurosci 20(5):674–680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Asari S, Itakura S, Ferreri K, Liu CP, Kuroda Y, Kandeel F, Mullen Y (2009) Mesenchymal stem cells suppress B-cell terminal differentiation. Exp Hematol 37(5):604–615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Tabera S, Perez-Simon JA, Diez-Campelo M, Sanchez-Abarca LI, Blanco B, Lopez A, Benito A, Ocio E, Sanchez-Guijo FM, Canizo C, San Miguel JF (2008) The effect of mesenchymal stem cells on the viability, proliferation and differentiation of B-lymphocytes. Haematologica 93(9):1301–1309

    Article  CAS  PubMed  Google Scholar 

  51. Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, Risso M, Gualandi F, Mancardi GL, Pistoia V, Uccelli A (2006) Human mesenchymal stem cells modulate B-cell functions. Blood 107(1):367–372

    Article  CAS  PubMed  Google Scholar 

  52. Luk F, Carreras-Planella L, Korevaar SS, de Witte SFH, Borras FE, Betjes MGH, Baan CC, Hoogduijn MJ, Franquesa M (2017) Inflammatory conditions dictate the effect of mesenchymal stem or stromal cells on B cell function. Front Immunol 8:1042

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Luz-Crawford P, Djouad F, Toupet K, Bony C, Franquesa M, Hoogduijn MJ, Jorgensen C, Noel D (2016) Mesenchymal stem cell-derived interleukin 1 receptor antagonist promotes macrophage polarization and inhibits B cell differentiation. Stem Cells 34(2):483–492

    Article  CAS  PubMed  Google Scholar 

  54. Schena F, Gambini C, Gregorio A, Mosconi M, Reverberi D, Gattorno M, Casazza S, Uccelli A, Moretta L, Martini A, Traggiai E (2010) Interferon-gamma-dependent inhibition of B cell activation by bone marrow-derived mesenchymal stem cells in a murine model of systemic lupus erythematosus. Arthritis Rheum 62(9):2776–2786

    Article  CAS  PubMed  Google Scholar 

  55. Comoli P, Ginevri F, Maccario R, Avanzini MA, Marconi M, Groff A, Cometa A, Cioni M, Porretti L, Barberi W, Frassoni F, Locatelli F (2008) Human mesenchymal stem cells inhibit antibody production induced in vitro by allostimulation. Nephrol Dial Transplant 23(4):1196–1202

    Article  CAS  PubMed  Google Scholar 

  56. Rosser EC, Mauri C (2015) Regulatory B cells: origin, phenotype, and function. Immunity 42(4):607–612

    Article  CAS  PubMed  Google Scholar 

  57. Franquesa M, Mensah FK, Huizinga R, Strini T, Boon L, Lombardo E, DelaRosa O, Laman JD, Grinyo JM, Weimar W, Betjes MG, Baan CC, Hoogduijn MJ (2015) Human adipose tissue-derived mesenchymal stem cells abrogate plasmablast formation and induce regulatory B cells independently of T helper cells. Stem Cells 33(3):880–891

    Article  CAS  PubMed  Google Scholar 

  58. 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(4):1484–1490

    Article  CAS  PubMed  Google Scholar 

  59. 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  CAS  PubMed  Google Scholar 

  60. Beyth S, Borovsky Z, Mevorach D, Liebergall M, Gazit Z, Aslan H, Galun E, Rachmilewitz J (2005) Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood 105(5):2214–2219

    Article  CAS  PubMed  Google Scholar 

  61. Djouad F, Charbonnier LM, Bouffi C, Louis-Plence P, Bony C, Apparailly F, Cantos C, Jorgensen C, Noel D (2007) Mesenchymal stem cells inhibit the differentiation of dendritic cells through an interleukin-6-dependent mechanism. Stem Cells 25(8):2025–2032

    Article  CAS  PubMed  Google Scholar 

  62. Chiesa S, Morbelli S, Morando S, Massollo M, Marini C, Bertoni A, Frassoni F, Bartolome ST, Sambuceti G, Traggiai E, Uccelli A (2011) Mesenchymal stem cells impair in vivo T-cell priming by dendritic cells. Proc Natl Acad Sci U S A 108(42):17384–17389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Zhang W, Ge W, Li C, You S, Liao L, Han Q, Deng W, Zhao RC (2004) Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells. Stem Cells Dev 13(3):263–271

    Article  CAS  PubMed  Google Scholar 

  64. Zhang B, Liu R, Shi D, Liu X, Chen Y, Dou X, Zhu X, Lu C, Liang W, Liao L, Zenke M, Zhao RC (2009) Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population. Blood 113(1):46–57

    Article  CAS  PubMed  Google Scholar 

  65. Kim J, Hematti P (2009) Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages. Exp Hematol 37(12):1445–1453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Martinez FO, Helming L, Gordon S (2009) Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol 27:451–483

    Article  CAS  PubMed  Google Scholar 

  67. Maggini J, Mirkin G, Bognanni I, Holmberg J, Piazzon IM, Nepomnaschy I, Costa H, Canones C, Raiden S, Vermeulen M, Geffner JR (2010) Mouse bone marrow-derived mesenchymal stromal cells turn activated macrophages into a regulatory-like profile. PLoS One 5(2):e9252

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Francois M, Romieu-Mourez R, Li M, Galipeau J (2012) Human MSC suppression correlates with cytokine induction of indoleamine 2,3-dioxygenase and bystander M2 macrophage differentiation. Mol Ther 20(1):187–195

    Article  CAS  PubMed  Google Scholar 

  69. Cho DI, Kim MR, Jeong HY, Jeong HC, Jeong MH, Yoon SH, Kim YS, Ahn Y (2014) Mesenchymal stem cells reciprocally regulate the M1/M2 balance in mouse bone marrow-derived macrophages. Exp Mol Med 46:e70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Nakajima H, Uchida K, Guerrero AR, Watanabe S, Sugita D, Takeura N, Yoshida A, Long G, Wright KT, Johnson WE, Baba H (2012) Transplantation of mesenchymal stem cells promotes an alternative pathway of macrophage activation and functional recovery after spinal cord injury. J Neurotrauma 29(8):1614–1625

    Article  PubMed  PubMed Central  Google Scholar 

  71. Brown JM, Nemeth K, Kushnir-Sukhov NM, Metcalfe DD, Mezey E (2011) Bone marrow stromal cells inhibit mast cell function via a COX2-dependent mechanism. Clin Exp Allergy 41(4):526–534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Kim HS, Yun JW, Shin TH, Lee SH, Lee BC, Yu KR, Seo Y, Lee S, Kang TW, Choi SW, Seo KW, Kang KS (2015) Human umbilical cord blood mesenchymal stem cell-derived PGE2 and TGF-beta1 alleviate atopic dermatitis by reducing mast cell degranulation. Stem Cells 33(4):1254–1266

    Article  CAS  PubMed  Google Scholar 

  73. Liu J, Kuwabara A, Kamio Y, Hu S, Park J, Hashimoto T, Lee JW (2016) Human mesenchymal stem cell-derived microvesicles prevent the rupture of intracranial aneurysm in part by suppression of mast cell activation via a PGE2-dependent mechanism. Stem Cells 34(12):2943–2955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Jiang D, Muschhammer J, Qi Y, Kugler A, de Vries JC, Saffarzadeh M, Sindrilaru A, Beken SV, Wlaschek M, Kluth MA, Ganss C, Frank NY, Frank MH, Preissner KT, Scharffetter-Kochanek K (2016) Suppression of neutrophil-mediated tissue damage-a novel skill of mesenchymal stem cells. Stem Cells 34(9):2393–2406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Raffaghello L, Bianchi G, Bertolotto M, Montecucco F, Busca A, Dallegri F, Ottonello L, Pistoia V (2008) Human mesenchymal stem cells inhibit neutrophil apoptosis: a model for neutrophil preservation in the bone marrow niche. Stem Cells 26(1):151–162

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Cho KA, Lee JK, Kim YH, Park M, Woo SY, Ryu KH (2017) Mesenchymal stem cells ameliorate B-cell-mediated immune responses and increase IL-10-expressing regulatory B cells in an EBI3-dependent manner. Cell Mol Immunol 14:895–908

    Article  CAS  Google Scholar 

  78. Ribeiro A, Laranjeira P, Mendes S, Velada I, Leite C, Andrade P, Santos F, Henriques A, Graos M, Cardoso CM, Martinho A, Pais M, da Silva CL, Cabral J, Trindade H, Paiva A (2013) 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 4(5):125

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Krampera M (2011) Mesenchymal stromal cell ‘licensing’: a multistep process. Leukemia 25(9):1408–1414

    Article  CAS  PubMed  Google Scholar 

  80. Smith CL, Chaichana KL, Lee YM, Lin B, Stanko KM, O’Donnell T, Gupta S, Shah SR, Wang J, Wijesekera O, Delannoy M, Levchenko A, Quinones-Hinojosa A (2015) Pre-exposure of human adipose mesenchymal stem cells to soluble factors enhances their homing to brain cancer. Stem Cells Transl Med 4(3):239–251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Rossnagl S, Ghura H, Groth C, Altrock E, Jakob F, Schott S, Wimberger P, Link T, Kuhlmann JD, Stenzl A, Hennenlotter J, Todenhofer T, Rojewski M, Bieback K, Nakchbandi IA (2018) A subpopulation of stromal cells controls cancer cell homing to the bone marrow. Cancer Res 78(1):129–142

    Article  CAS  PubMed  Google Scholar 

  82. De Becker A, Riet IV (2016) Homing and migration of mesenchymal stromal cells: how to improve the efficacy of cell therapy? World J Stem Cells 8(3):73–87

    Article  PubMed  PubMed Central  Google Scholar 

  83. Cornelissen AS, Maijenburg MW, Nolte MA, Voermans C (2015) Organ-specific migration of mesenchymal stromal cells: who, when, where and why? Immunol Lett 168(2):159–169

    Article  CAS  PubMed  Google Scholar 

  84. Mansilla E, Marin GH, Drago H, Sturla F, Salas E, Gardiner C, Bossi S, Lamonega R, Guzman A, Nunez A, Gil MA, Piccinelli G, Ibar R, Soratti C (2006) Bloodstream cells phenotypically identical to human mesenchymal bone marrow stem cells circulate in large amounts under the influence of acute large skin damage: new evidence for their use in regenerative medicine. Transplant Proc 38(3):967–969

    Article  CAS  PubMed  Google Scholar 

  85. Hocking AM (2015) The role of chemokines in mesenchymal stem cell homing to wounds. Adv Wound Care 4(11):623–630

    Article  Google Scholar 

  86. Jin W, Liang X, Brooks A, Futrega K, Liu X, Doran MR, Simpson MJ, Roberts MS, Wang H (2018) Modelling of the SDF-1/CXCR4 regulated in vivo homing of therapeutic mesenchymal stem/stromal cells in mice. Peer J 6:e6072

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  87. Matsuno H, Yudoh K, Katayama R, Nakazawa F, Uzuki M, Sawai T, Yonezawa T, Saeki Y, Panayi GS, Pitzalis C, Kimura T (2002) The role of TNF-alpha in the pathogenesis of inflammation and joint destruction in rheumatoid arthritis (RA): a study using a human RA/SCID mouse chimera. Rheumatology 41(3):329–337

    Article  CAS  PubMed  Google Scholar 

  88. Marotte H, Cimaz R (2014) Etanercept - TNF receptor and IgG1 fc fusion protein: is it different from other TNF blockers? Expert Opin Biol Ther 14(5):569–572

    Article  CAS  PubMed  Google Scholar 

  89. Liu LN, Wang G, Hendricks K, Lee K, Bohnlein E, Junker U, Mosca JD (2013) Comparison of drug and cell-based delivery: engineered adult mesenchymal stem cells expressing soluble tumor necrosis factor receptor II prevent arthritis in mouse and rat animal models. Stem Cells Transl Med 2(5):362–375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Munoz JL, Bliss SA, Greco SJ, Ramkissoon SH, Ligon KL, Rameshwar P (2013) Delivery of functional anti-miR-9 by mesenchymal stem cell-derived exosomes to glioblastoma Multiforme cells conferred Chemosensitivity. Mol Ther Nucleic Acids 2:e126

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Seo SH, Kim KS, Park SH, Suh YS, Kim SJ, Jeun SS, Sung YC (2011) The effects of mesenchymal stem cells injected via different routes on modified IL-12-mediated antitumor activity. Gene Ther 18(5):488–495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Stagg J, Lejeune L, Paquin A, Galipeau J (2004) Marrow stromal cells for interleukin-2 delivery in cancer immunotherapy. Hum Gene Ther 15(6):597–608

    Article  CAS  PubMed  Google Scholar 

  93. Studeny M, Marini FC, Champlin RE, Zompetta C, Fidler IJ, Andreeff M (2002) Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Res 62(13):3603–3608

    CAS  PubMed  Google Scholar 

  94. Mendelson A, Frenette PS (2014) Hematopoietic stem cell niche maintenance during homeostasis and regeneration. Nat Med 20(8):833–846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Sugiyama T, Kohara H, Noda M, Nagasawa T (2006) Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 25(6):977–988

    Article  CAS  PubMed  Google Scholar 

  96. Zou L, Chen Q, Quanbeck Z, Bechtold JE, Kaufman DS (2016) Angiogenic activity mediates bone repair from human pluripotent stem cell-derived osteogenic cells. Sci Rep 6:22868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Li GC, Zhang HW, Zhao QC, Sun LI, Yang JJ, Hong L, Feng F, Cai L (2016) Mesenchymal stem cells promote tumor angiogenesis via the action of transforming growth factor beta1. Oncol Lett 11(2):1089–1094

    Article  CAS  PubMed  Google Scholar 

  98. Gong M, Yu B, Wang J, Wang Y, Liu M, Paul C, Millard RW, Xiao DS, Ashraf M, Xu M (2017) Mesenchymal stem cells release exosomes that transfer miRNAs to endothelial cells and promote angiogenesis. Oncotarget 8(28):45200–45212

    Article  PubMed  PubMed Central  Google Scholar 

  99. Merino-Gonzalez C, Zuniga FA, Escudero C, Ormazabal V, Reyes C, Nova-Lamperti E, Salomon C, Aguayo C (2016) Mesenchymal stem cell-derived extracellular vesicles promote angiogenesis: potencial clinical application. Front Physiol 7:24

    Article  PubMed  PubMed Central  Google Scholar 

  100. Yu YS, Shen ZY, Ye WX, Huang HY, Hua F, Chen YH, Chen K, Lao WJ, Tao L (2010) AKT-modified autologous intracoronary mesenchymal stem cells prevent remodeling and repair in swine infarcted myocardium. Chin Med J 123(13):1702–1708

    CAS  PubMed  Google Scholar 

  101. Martin I, De Boer J, Sensebe L, MSC Committee of the International Society for Cellular Therapy (2016) A relativity concept in mesenchymal stromal cell manufacturing. Cytotherapy 18(5):613–620

    Article  CAS  PubMed  Google Scholar 

  102. Morandi F, Raffaghello L, Bianchi G, Meloni F, Salis A, Millo E, Ferrone S, Barnaba V, Pistoia V (2008) Immunogenicity of human mesenchymal stem cells in HLA-class I-restricted T-cell responses against viral or tumor-associated antigens. Stem Cells 26(5):1275–1287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Najima Y (2017) Mesenchymal stem cells for treatment of graft-versus-host disease. Rinsho Ketsueki 58(12):2440–2449

    PubMed  Google Scholar 

  104. Amorin B, Alegretti AP, Valim V, Pezzi A, Laureano AM, da Silva MA, Wieck A, Silla L (2014) Mesenchymal stem cell therapy and acute graft-versus-host disease: a review. Hum Cell 27(4):137–150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Yagi H, Soto-Gutierrez A, Parekkadan B, Kitagawa Y, Tompkins RG, Kobayashi N, Yarmush ML (2010) Mesenchymal stem cells: mechanisms of immunomodulation and homing. Cell Transplant 19(6):667–679

    Article  PubMed  Google Scholar 

  106. Baumgart DC, Sandborn WJ (2012) Crohn’s disease. Lancet 380(9853):1590–1605

    Article  PubMed  Google Scholar 

  107. Dalal J, Gandy K, Domen J (2012) Role of mesenchymal stem cell therapy in Crohn’s disease. Pediatr Res 71(4 Pt 2):445–451

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA

    Adam Eljarrah, Marina Gergues, Piotr W. Pobiarzyn & Oleta A. Sandiford

  2. Rutgers School of Graduate School at New Jersey Medical School, Newark, NJ, USA

    Adam Eljarrah, Marina Gergues, Piotr W. Pobiarzyn & Oleta A. Sandiford

  3. Department of Medicine – Division of Hematology/Oncology, New Jersey Medical School, Rutgers School of Biomedical Health Science, Newark, NJ, USA

    Pranela Rameshwar

Authors
  1. Adam Eljarrah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marina Gergues
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Piotr W. Pobiarzyn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Oleta A. Sandiford
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pranela Rameshwar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pranela Rameshwar .

Editor information

Editors and Affiliations

  1. Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA

    Mariusz Z. Ratajczak

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Eljarrah, A., Gergues, M., Pobiarzyn, P.W., Sandiford, O.A., Rameshwar, P. (2019). Therapeutic Potential of Mesenchymal Stem Cells in Immune-Mediated Diseases. In: Ratajczak, M. (eds) Stem Cells. Advances in Experimental Medicine and Biology, vol 1201. Springer, Cham. https://doi.org/10.1007/978-3-030-31206-0_5

Download citation

Publish with us

Policies and ethics

Search

Navigation