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Immuno-Therapeutic Potential of Haematopoietic and Mesenchymal Stem Cell Transplantation in MS

  • Chapter
  • First Online:
Molecular Basis of Multiple Sclerosis

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 51))

Abstract

In the last few years there has been extraordinary progress in the field of stem cell research. Two types of stem cells populate the bone marrow: haematopoietic stem/progenitor cells (HSC) and mesenchymal stem cells (MSC). The capacity of HSC to repopulate the blood has been known and exploited therapeutically for at least four decades. Today, haematopoietic stem cell transplantation (HSCT) holds a firm place in the therapy of some haematological malignancies, and a potential role of HSCT for treatment of severe autoimmune diseases has been explored in small-scale clinical studies. Multiple sclerosis (MS) is the noncancerous immune mediated disease for which the greatest number of transplants has been performed to date. The results of clinical studies are double-faced: on the one hand, HSCT has demonstrated powerful effects on acute inflammation, arresting the development of focal CNS lesions and clinical relapses; on the other hand, the treatment did not arrest chronic worsening of disability in most patients with secondary progressive MS, suggesting limited or no beneficial effects on the chronic processes causing progressive disability. MSC are a more recent addition to the range of experimental therapies being developed to treat MS. While interest in MSC usage was originally raised by their potential capacity to differentiate into different cell lineages, recent work showing their interesting immunological properties has led to a revised concept, envisioning their utilization for immuno-modulatory purposes. In this review we will summarize the current clinical and experimental evidence on HSC and MSC and outline some key questions warranting further investigation in this exciting research area.

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References

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

    Google Scholar 

  • Almeida-Porada G, Porada CD, Tran N, Zanjani ED (2000) Cotransplantation of human stromal cell progenitors into preimmune fetal sheep results in early appearance of human donor cells in circulation and boosts cell levels in bone marrow at later time points after transplantation. Blood 95:3620–3627.

    Google Scholar 

  • Augello A, Tasso R, Negrini SM, Amateis A, Indiveri F, Cancedda R, Pennesi G (2005) Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed death 1 pathway. Eur J Immunol 35:1482–1490.

    Google Scholar 

  • Ball LM, Bernardo ME, Roelofs H, Lankester A, Cometa A, Egeler RM, Locatelli F, Fibbe WE (2007) Cotransplantation of ex vivo expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation. Blood 110(7):2764–2767

    Article  PubMed  CAS  Google Scholar 

  • Banati RB, Newcombe J, Gunn RN, Cagnin A, Turkheimer F, Heppner F, Price G, Wegner F, Giovannoni G, Miller DH et al (2000) The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity. Brain 123(Pt 11):2321–2337

    Article  PubMed  Google Scholar 

  • Bang OY, Lee JS, Lee PH, Lee G (2005) Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 57(6):874–882

    Article  PubMed  Google Scholar 

  • Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R (2002) Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 30(1):42–48

    Article  PubMed  Google Scholar 

  • Bernardo ME, Zaffaroni N, Novara F, Cometa AM, Avanzini MA, Moretta A, Montagna D, Maccario R, Villa R, Daidone MG, Zuffardi O, Locatelli F (2007) Human bone marrow derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exhibit telomere maintenance mechanisms. Cancer Res 67:9142–9149.

    Google Scholar 

  • Berzins SP, Uldrich AP, Sutherland JS, Gill J, Miller JF, Godfrey DI, Boyd RL (2002) Thymic regeneration: teaching an old immune system new tricks. Trends Mol Med 8(10):469–476

    Article  PubMed  CAS  Google Scholar 

  • 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 105:2214–2219.

    Google Scholar 

  • Bianco P, Gehron Robey P (2000) Marrow stromal stem cells. J Clin Invest 105(12):1663–1668

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Bielekova B, Sung MH, Kadom N, Simon R, McFarland H, Martin R (2004) Expansion and functional relevance of high-avidity myelin-specific CD4+ T cells in multiple sclerosis. J Immunol 172(6):3893–3904

    Article  PubMed  CAS  Google Scholar 

  • Bocelli-Tyndall C, Bracci L, Spagnoli G, Braccini A, Bouchenaki M, Ceredig R, Pistoia V, Martin I, Tyndall A (2006) Bone marrow mesenchymal stromal cells (BM-MSCs) from healthy donors and auto-immune disease patients reduce the proliferation of autologous- and allogeneic-stimulated lymphocytes in vitro. Rheumatology 46(3):403–408

    Article  PubMed  Google Scholar 

  • Brinkman DM, Jol-van der Zijde CM, Ten Dam MM, Te Boekhorst PA, Ten Cate R, Wulffraat NM, Hintzen RQ, Vossen JM, van Tol MJ (2007) Resetting the adaptive immune system after autologous stem cell transplantation: lessons from responses to vaccines. J Clin Immunol 27:647–658

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Burt RK, Traynor AE, Pope R, Schroeder J, Cohen B, Karlin KH, Lobeck L, Goolsby C, Rowlings P, Davis FA et al (1998) Treatment of autoimmune disease by intense immunosuppressive conditioning and autologous hematopoietic stem cell transplantation. Blood 92(10):3505–3514

    PubMed  CAS  Google Scholar 

  • Carreras E, Saiz A, Marin P, Martinez C, Rovira M, Villamor N, Aymerich M, Lozano M, Fernandez-Aviles F, Urbano-Izpizua A et al (2003) CD34 + selected autologous peripheral blood stem cell transplantation for multiple sclerosis: report of toxicity and treatment results at one year of follow-up in 15 patients. Haematologica 88(3):306–314

    PubMed  Google Scholar 

  • 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 110:3691–3694.

    Google Scholar 

  • Chopp M, Li Y (2002) Treatment of neural injury with marrow stromal cells. Lancet Neurol 1(2):92–100

    Article  PubMed  Google Scholar 

  • Coles AJ, Cox A, Le Page E, Jones J, Trip SA, Deans J, Seaman S, Miller DH, Hale G, Waldmann H et al (2005) The window of therapeutic opportunity in multiple sclerosis Evidence from monoclonal antibody therapy. J Neurol 27:27

    Google Scholar 

  • 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 107:367–372.

    Google Scholar 

  • de Kleer I, Vastert B, Klein M, Teklenburg G, Arkesteijn G, Puga Yung G, Albani S, Kuis W, Wulffraat N, Prakken B (2005) Autologous stem cell transplantation for autoimmunity induces immunologic self-tolerance by reprogramming autoreactive T-cells and restoring the CD4+ CD25+ immune regulatory network. Blood 1:1

    Google Scholar 

  • De Kleer IM, Brinkman DM, Ferster A, Abinun M, Quartier P, Van Der Net J, Ten Cate R, Wedderburn LR, Horneff G, Oppermann J et al (2004) Autologous stem cell transplantation for refractory juvenile idiopathic arthritis: analysis of clinical effects, mortality, and transplant related morbidity. Ann Rheum Dis 63(10):1318–1326

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • DeLorenze GN, Munger KL, Lennette ET, Orentreich N, Vogelman JH, Ascherio A (2006) Epstein-Barr virus and multiple sclerosis: evidence of association from a prospective study with long-term follow-up. Arch Neurol 63(6):839–844

    Article  PubMed  Google Scholar 

  • 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 99:3838–3843.

    Google Scholar 

  • Djouad F, Plence P, Bony C, Tropel P, Apparailly F, Sany J, Noel D, Jorgensen C (2003) Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood 102(10):3837–3844

    Article  PubMed  CAS  Google Scholar 

  • Douek DC, Koup RA (2000) Evidence for thymic function in the elderly. Vaccine 18(16):1638–1641

    Article  PubMed  CAS  Google Scholar 

  • Douek DC, Vescio RA, Betts MR, Brenchley JM, Hill BJ, Zhang L, Berenson JR, Collins RH, Koup RA (2000) Assessment of thymic output in adults after haematopoietic stem-cell transplantation and prediction of T-cell reconstitution. Lancet 355(9218):1875–1881

    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.

    Google Scholar 

  • Farge D, Henegar C, Carmagnat M, Daneshpouy M, Marjanovic Z, Rabian C, Ilie D, Douay C, Mounier N, Clave E et al (2005) Analysis of immune reconstitution after autologous bone marrow transplantation in systemic sclerosis. Arthritis Rheum 52(5):1555–1563

    Article  PubMed  CAS  Google Scholar 

  • Fassas A, Passweg JR, Anagnostopoulos A, Kazis A, Kozak T, Havrdova E, Carreras E, Graus F, Kashyap A, Openshaw H et al (2002) Hematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study. J Neurol 249(8):1088–1097

    CAS  Google Scholar 

  • Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF, Keiliss-Borok IV (1974) Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation 17:331–340.

    Google Scholar 

  • Gerdoni E, Gallo B, Casazza S, Musio S, Bonanni I, Pedemonte E, Mantegazza R, Frassoni F, Mancardi G, Pedotti R et al (2007) Mesenchymal stem cells effectively modulate pathogenic immune response in experimental autoimmune encephalomyelitis. Ann Neurol 61(3):219–227

    Article  PubMed  CAS  Google Scholar 

  • Gieseke F, Schutt B, Viebahn S, Koscielniak E, Friedrich W, Handgretinger R, Muller I (2007) Human multipotent mesenchymal stromal cells inhibit proliferation of PBMCs independently of IFNgammaR1 signaling and IDO expression. Blood 110:2197–2200. 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.

    Google Scholar 

  • Guillaume T, Rubinstein DB, Symann M (1998) Immune reconstitution and immunotherapy after autologous hematopoietic stem cell transplantation. Blood 92(5):1471–1490

    PubMed  CAS  Google Scholar 

  • Hakim FT, Memon SA, Cepeda R, Jones EC, Chow CK, Kasten-Sportes C, Odom J, Vance BA, Christensen BL, Mackall CL et al (2005) Age-dependent incidence, time course, and consequences of thymic renewal in adults. J Clin Invest 115(4):930–939

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Healey KM, Pavletic SZ, Al-Omaishi J, Leuschen MP, Pirruccello SJ, Filipi ML, Enke C, Ursick MM, Hahn F, Bowen JD, Nash RA (2004) Discordant functional and inflammatory parameters in multiple sclerosis patients after autologous haematopoietic stem cell transplantation. Mult Scler 10:284–289.

    Google Scholar 

  • Herrmann MM, Gaertner S, Stadelmann C, van den Brandt J, Boscke R, Budach W, Reichardt HM, Weissert R (2005) Tolerance induction by bone marrow transplantation in a multiple sclerosis model. Blood 106(5):1875–1883

    Article  PubMed  CAS  Google Scholar 

  • Hofstetter CP, Schwarz EJ, Hess D, Widenfalk J, El Manira A, Prockop DJ, Olson L (2002) Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc Natl Acad Sci U S A 99:2199–2204.

    Google Scholar 

  • Horwitz E, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini F, Deans R, Krause D, Keating A (2005) Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy 7(5):393–395

    Article  PubMed  CAS  Google Scholar 

  • Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M, Sussman M, Orchard P, Marx JC, Pyeritz RE, Brenner MK (1999) Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 5:309–313. Jiang XX, Zhang Y, Liu B, Zhang SX, Wu Y, Yu XD, Mao N (2005) Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood 105:4120–4126.

    Google Scholar 

  • Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449(7162):557–563

    Article  PubMed  CAS  Google Scholar 

  • Kastrinaki MC, Sidiropoulos P, Roche S, Ringe J, Lehmann S, Kritikos H, Vlahava VM, Delorme B, Eliopoulos G, Jorgensen C et al (2007) Functional, molecular and proteomic characterization of bone marrow mesenchymal stem cells in rheumatoid arthritis. Ann Rheum Dis 67:741–749

    Article  PubMed  Google Scholar 

  • Keating A (2006) Mesenchymal stromal cells. Curr Opin Hematol 13:419–425. Koc ON, Day J, Nieder M, Gerson SL, Lazarus HM, Krivit W (2002/8) Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH). Bone Marrow Transplant 30:215–222.

    Google Scholar 

  • Koehne G, Zeller W, Stockschlaeder M, Zander AR (1997) Phenotype of lymphocyte subsets after autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 19(2):149–156

    Article  PubMed  CAS  Google Scholar 

  • Kopen GC, Prockop DJ, Phinney DG (1999) Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc.Natl.Acad.Sci U.S.A 96:10711–10716.

    Google Scholar 

  • Kozak T, Havrdova E, Pit’ha J, Gregora E, Pytlik R, Maaloufova J, Mareckova H, Kobylka P, Vodvarkova S (2000) High-dose immunosuppressive therapy with PBPC support in the treatment of poor risk multiple sclerosis. Bone Marrow Transplant 25(5):525–531

    Article  PubMed  CAS  Google Scholar 

  • Krampera M, Glennie S, Dyson J, Scott D, Laylor R, Simpson E, Dazzi F (2003) Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood 101:3722–3729.

    Google Scholar 

  • Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O (2004) Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 363:1439–1441.

    Google Scholar 

  • Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringden O (2008) Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371:1579–1586.

    Google Scholar 

  • Li Y, Chen J, Chen XG, Wang L, Gautam SC, Xu YX, Katakowski M, Zhang LJ, Lu M, Janakiraman N et al (2002) Human marrow stromal cell therapy for stroke in rat: Neurotrophins and functional recovery. Neurology 59(4):514–523

    Article  PubMed  CAS  Google Scholar 

  • Maccario R, Podesta M, Moretta A, Cometa A, Comoli P, Montagna D, Daudt L, Ibatici A, Piaggio G, Pozzi S et al (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

    PubMed  CAS  Google Scholar 

  • Malphettes M, Carcelain G, Saint-Mezard P, Leblond V, Altes HK, Marolleau JP, Debre P, Brouet JC, Fermand JP, Autran B (2003) Evidence for naive T-cell repopulation despite thymus irradiation after autologous transplantation in adults with multiple myeloma: role of ex vivo CD34+ selection and age. Blood 101(5):1891–1897

    Article  PubMed  CAS  Google Scholar 

  • Mancardi G, Saccardi R (2008) Autologous haematopoietic stem-cell transplantation in multiple sclerosis. Lancet Neurol 7(7):626–636

    Article  PubMed  Google Scholar 

  • Mancardi GL, Saccardi R, Filippi M, Gualandi F, Murialdo A, Inglese M, Marrosu MG, Meucci G, Massacesi L, Lugaresi A et al (2001) Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI activity in MS. Neurology 57(1):62–68

    Article  PubMed  CAS  Google Scholar 

  • Mazzanti B, Aldinucci A, Biagioli T, Barilaro A, Urbani A, Dal Pozzo S, Amato M, Siracusa G, Crescioli C, Manuelli C et al (2008) Differences in mesenchymal stem cell cytokine profiles between MS patients and healthy donors: Implication for assessment of disease activity and treatment. J Neuroimmunol 199(1–2):142–150

    Google Scholar 

  • Meirelles LdS, Chagastelles PC, Nardi NB (2006) Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci 119(11):2204–2213

    Article  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(12):4619–4621

    Article  PubMed  CAS  Google Scholar 

  • Metz I, Lucchinetti CF, Openshaw H, Garcia-Merino A, Lassmann H, Freedman M, Azzarelli B, Kolar OJ, Atkins HL, Bruck W (2006) Multiple sclerosis pathology after autologous stem cell transplantation: ongoing demyelination and neurodegeneration despite suppressed inflammation. Mult Scler 12:S9

    Google Scholar 

  • Munoz JR, Stoutenger BR, Robinson AP, Spees JL, Prockop DJ (2005) Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice. Proc Natl Acad Sci U S A 102(50):18171–18176

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Muraro PA, Douek DC (2006) Renewing the T cell repertoire to arrest autoimmune aggression. Trends Immunol 27:61–67.

    Google Scholar 

  • Muraro PA, Douek DC, Packer A, Chung K, Guenaga FJ, Cassiani-Ingoni R, Campbell C, Memon S, Nagle JW, Hakim FT et al (2005) Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J Exp Med 201(5):805–816

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Muraro PA, Pette M, Bielekova B, McFarland HF, Martin R (2000) Human Autoreactive CD4+ T Cells from Naive CD45RA+ and Memory CD45RO+ Subsets Differ with Respect to Epitope Specificity and Functional Antigen Avidity. J Immunol 164:5474–5481

    Article  PubMed  CAS  Google Scholar 

  • Muraro PA, Van Laar JM, Illei G, Pavletic S (2008) Hematopoietic stem cell transplantation for autoimmune disorders. In: Barrett AJ, Treleaven JG (eds) Hematopoietic stem cell transplantation in clinical practice. Churchill Livingstone, Oxford, pp 197–210

    Google Scholar 

  • Nash RA, Bowen JD, McSweeney PA, Pavletic SZ, Maravilla KR, Park MS, Storek J, Sullivan KM, Al-Omaishi J, Corboy JR et al (2003) High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis. Blood 102(7):2364–2372

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Nauta AJ, Fibbe WE (2007) Immunomodulatory properties of mesenchymal stromal cells. Blood 110:3499–3506.

    Google Scholar 

  • Nauta AJ, Westerhuis G, Kruisselbrink AB, Lurvink EG, Willemze R, Fibbe WE (2006) 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.

    Google Scholar 

  • Okamoto R, Yajima T, Yamazaki M, Kanai T, Mukai M, Okamoto S, Ikeda Y, Hibi T, Inazawa J, Watanabe M (2002/9) Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract. Nat Med 8(9):1011–1017

    Article  PubMed  CAS  Google Scholar 

  • Openshaw H, Lund BT, Kashyap A, Atkinson R, Sniecinski I, Weiner LP, Forman S (2000) Peripheral blood stem cell transplantation in multiple sclerosis with busulfan and cyclophosphamide conditioning: report of toxicity and immunological monitoring. Biol Blood Marrow Transplant 6:563–575.

    Google Scholar 

  • Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410:701–705.

    Google Scholar 

  • Papadaki HA, Tsagournisakis M, Mastorodemos V, Pontikoglou C, Damianaki A, Pyrovolaki K, Stamatopoulos K, Fassas A, Plaitakis A, Eliopoulos GD (2005) Normal bone marrow hematopoietic stem cell reserves and normal stromal cell function support the use of autologous stem cell transplantation in patients with multiple sclerosis. Bone Marrow Transplant 36:1053–1063.

    Google Scholar 

  • Passweg JR, Rabusin M, Musso M, Beguin Y, Cesaro S, Ehninger G, Espigado I, Iriondo A, Jost L, Koza V et al (2004) Haematopoetic stem cell transplantation for refractory autoimmune cytopenia. Br J Haematol 125(6):749–755

    Article  PubMed  CAS  Google Scholar 

  • Pedemonte E, Benvenuto F, Casazza S, Mancardi G, Oksenberg JR, Uccelli A, Baranzini SE (2007) The molecular signature of therapeutic mesenchymal stem cells exposes the architecture of the hematopoietic stem cell niche synapse. BMC Genomics 8:65.

    Google Scholar 

  • Pereira RF, Halford KW, O’Hara MD, Leeper DB, Sokolov BP, Pollard MD, Bagasra O, Prockop DJ (1995) Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice. Proc Natl Acad Sci U S A 92(11):4857–4861

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Phinney DG, Hill K, Michelson C, Dutreil M, Hughes C, Humphries S, Wilkinson R, Baddoo M, Bayly E (2006) Biological activities encoded by the murine mesenchymal stem cell transcriptome provide a basis for their developmental potential and broad therapeutic efficacy. Stem Cells 24(1):186–198

    Article  PubMed  Google Scholar 

  • Phinney DG, Prockop DJ (2007) Concise Review: Mesenchymal Stem/Multi-Potent Stromal Cells (MSCs): The State of Transdifferentiation and Modes of Tissue Repair – Current Views. Stem Cells 25(11):2896–2902

    Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147.

    Google Scholar 

  • Poggi A, Prevosto C, Massaro AM, Negrini S, Urbani S, Pierri I, Saccardi R, Gobbi M, Zocchi MR (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.

    Google Scholar 

  • Prevosto C, Zancolli M, Canevali P, Zocchi MR, Poggi A (2007) Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem cell-lymphocyte interaction. Haematologica 92:881–888.

    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 83:71–76.

    Google Scholar 

  • Rasmusson I, Ringden O, Sundberg B, Le Blanc K (2005) Mesenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by different mechanisms. Exp.Cell Res. 305:33–41.

    Google Scholar 

  • Rivera FJ, Couillard-Despres S, Pedre X, Ploetz S, Caioni M, Lois C, Bogdahn U, Aigner L (2006) Mesenchymal stem cells instruct oligodendrogenic fate decision on adult neural stem cells. Stem Cells 24:2209–2219.

    Google Scholar 

  • Rosen O, Thiel A, Massenkeil G, Hiepe F, Haupl T, Radtke H, Burmester GR, Gromnica-Ihle E, Radbruch A, Arnold R (2000) Autologous stem-cell transplantation in refractory autoimmune diseases after in vivo immunoablation and ex vivo depletion of mononuclear cells. Arthritis Res 2:327–336

    Google Scholar 

  • Rubio D, Garcia-Castro J, Martin MC, de la FR, Cigudosa JC, Lloyd AC, Bernad A (2005) Spontaneous human adult stem cell transformation. Cancer Res. 65:3035–3039.

    Google Scholar 

  • Saccardi R, Mancardi GL, Solari A, Bosi A, Bruzzi P, Di Bartolomeo P, Donelli A, Filippi M, Guerrasio A, Gualandi F et al (2005) Autologous HSCT for severe progressive multiple sclerosis in a multicenter trial: impact on disease activity and quality of life. Blood 105(6):2601–2607

    Article  PubMed  CAS  Google Scholar 

  • Sacchetti B, Funari A, Michienzi S, Di Cesare S, Piersanti S, Saggio I, Tagliafico E, Ferrari S, Robey PG, Riminucci M, Bianco P (2007) Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131:324–336.

    Google Scholar 

  • Saiz A, Carreras E, Berenguer J, Yague J, Martinez C, Marin P, Rovira M, Pujol T, Arbizu T, Graus F (2001) MRI and CSF oligoclonal bands after autologous hematopoietic stem cell transplantation in MS. Neurology 56(8):1084–1089

    Article  PubMed  CAS  Google Scholar 

  • Samijn JP, te Boekhorst PA, Mondria T, van Doorn PA, Flach HZ, van der Meche FG, Cornelissen J, Hop WC, Lowenberg B, Hintzen RQ (2006) Intense T cell depletion followed by autologous bone marrow transplantation for severe multiple sclerosis. J Neurol Neurosurg Psychiatry 77(1):46–50

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Sato K, Ozaki K, Oh I, Meguro A, Hatanaka K, Nagai T, Muroi K, Ozawa K (2006) Nitric oxide plays a critical role in suppression of T cell proliferation by mesenchymal stem cells. Blood 109:228–234.

    Google Scholar 

  • Schofield R (1978) The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 4(1–2):7–25

    PubMed  CAS  Google Scholar 

  • 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 26:212–222.

    Google Scholar 

  • Shevach EM (2000) Regulatory T cells in autoimmmunity*. Annu Rev Immunol 18:423–449

    Article  PubMed  CAS  Google Scholar 

  • Shlomchik MJ, Craft JE, Mamula MJ (2001) From T to B and back again: positive feedback in systemic autoimmune disease. Nat Rev Immunol 1(2):147–153

    Article  PubMed  CAS  Google Scholar 

  • Slavin S, Kurkalli BG, Karussis D (2008) The potential use of adult stem cells for the treatment of multiple sclerosis and other neurodegenerative disorders. Clin Neurol Neurosurg 110:943–946.

    Google Scholar 

  • Snowden JA, Passweg J, Moore JJ, Milliken S, Cannell P, Van Laar J, Verburg R, Szer J, Taylor K, Joske D et al (2004) Autologous hemopoietic stem cell transplantation in severe rheumatoid arthritis: a report from the EBMT and ABMTR. J Rheumatol 31(3):482–488

    PubMed  Google Scholar 

  • Sospedra M, Martin R (2005) Immunology of multiple sclerosis. Annu Rev Immunol 23:683–747

    Article  PubMed  CAS  Google Scholar 

  • Sotiropoulou PA, Perez SA, Gritzapis AD, Baxevanis CN, Papamichail M (2006) Interactions Between Human Mesenchymal Stem Cells and Natural Killer Cells. Stem Cells 24:74–85.

    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 111:1327–1333.

    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.

    Google Scholar 

  • Storek J, Dawson MA, Maloney DG (2003) Correlation between the numbers of naive T cells infused with blood stem cell allografts and the counts of naive T cells after transplantation. Biol Blood Marrow Transplant 9(12):781–784

    Article  PubMed  Google Scholar 

  • Sun W, Popat U, Hutton G, Zang YC, Krance R, Carrum G, Land GA, Heslop H, Brenner M, Zhang JZ (2004) Characteristics of T-cell receptor repertoire and myelin-reactive T cells reconstituted from autologous haematopoietic stem-cell grafts in multiple sclerosis. Brain 127(Pt 5):996–1008

    Article  PubMed  Google Scholar 

  • Tolar J, Nauta AJ, Osborn MJ, Panoskaltsis Mortari A, McElmurry RT, Bell S, Xia L, Zhou N, Riddle M, Schroeder TM et al (2006) Sarcoma Derived from Cultured Mesenchymal Stem Cells. Stem Cells 25:371–379

    Article  PubMed  Google Scholar 

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

    Google Scholar 

  • Uccelli A, Moretta L, Pistoia V (2008) Mesenchymal stem cells: role in health and disease. Nat Rev Immunol 8:726–736

    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 

  • Verburg RJ, Kruize AA, van den Hoogen FH, Fibbe WE, Petersen EJ, Preijers F, Sont JK, Barge RM, Bijlsma JW, van de Putte LB et al (2001) High-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with rheumatoid arthritis: results of an open study to assess feasibility, safety, and efficacy. Arthritis Rheum 44(4):754–760

    Article  PubMed  CAS  Google Scholar 

  • Zappia E, Casazza S, Pedemonte E, Benvenuto F, Bonanni I, Gerdoni E, Giunti D, Ceravolo A, Cazzanti F, Frassoni F et al (2005) Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T cell anergy. Blood 106(5):1755–1761

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was partially supported by the National Institute for Health Research and by the Hammersmith Hospitals Research Trustees Committee (to P.A.M.).

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Authors and Affiliations

  1. Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College Building 560/Burlington Danes, Room E415, Imperial College London, 160 Du Cane Road, London, UK

    Paolo A. Muraro

  2. Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy

    Antonio Uccelli

  3. Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy

    Antonio Uccelli

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  1. Paolo A. Muraro
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  2. Antonio Uccelli
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Correspondence to Paolo A. Muraro .

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Editors and Affiliations

  1. Institut für Neuroimmunologie und, Klinische Multiple-Sklerose-Forschung, Universitätsklinikum Hamburg-Eppendorf, Falkenried 94, Hamburg, 20251, Germany

    Roland Martin

  2. , Clinical Department of Neurology, Innsbruck Medical University, Anichstrasse 35, Innsbruck, 6020, Austria

    Andreas Lutterotti

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Muraro, P.A., Uccelli, A. (2009). Immuno-Therapeutic Potential of Haematopoietic and Mesenchymal Stem Cell Transplantation in MS. In: Martin, R., Lutterotti, A. (eds) Molecular Basis of Multiple Sclerosis. Results and Problems in Cell Differentiation, vol 51. Springer, Berlin, Heidelberg. https://doi.org/10.1007/400_2008_14

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