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Haematopoietic Stem Cells for the Treatment of MS

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Multiple Sclerosis Immunology

Abstract

The last decade of research has achieved incredible advances in our understanding of stem cell biology. Amongst the best characterised types of stem cells are haematopoietic stem cells (HSC). Starting from the morphological description of bone marrow (BM)-resident cells in the early 1900s, studies on the physiological function of haematopoietic precursor cells have caught momentum in the 1960s and 1970s and have expanded exponentially following the increased availability of reagents and molecular methodologies in the 1980s and 1990s. In parallel, the clinical application of BM—and peripherally mobilised HSC—transplantation for haematological indications has been studied intensively in trials and applied in clinical practice. Since the mid-1990s, treatment of autoimmune disorders, including multiple sclerosis (MS), with autologous haematopoietic transplantation has been explored in clinical trials. More recently, an integrin-blocking antibody approved for treatment of MS has been shown to exert an effect on HSC recirculation as well as the expected effects on leucocyte trafficking.

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References

  • Alexander T, Thiel A, Rosen O, Massenkeil G, Sattler A et al (2009) Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system. Blood 113:214–223

    Article  PubMed  CAS  Google Scholar 

  • Anderson BE, McNiff JM, Matte C, Athanasiadis I, Shlomchik WD, Shlomchik MJ (2004) Recipient CD4+ T cells that survive irradiation regulate chronic graft-versus-host disease. Blood 104:1565–1573

    Article  PubMed  CAS  Google Scholar 

  • Anolik JH, Barnard J, Cappione A, Pugh-Bernard AE, Felgar RE et al (2004) Rituximab improves peripheral B cell abnormalities in human systemic lupus erythematosus. Arthritis Rheum 50:3580–3590

    Article  PubMed  CAS  Google Scholar 

  • Arai F, Hirao A, Ohmura M, Sato H, Matsuoka S et al (2004) Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 118:149–161

    Article  PubMed  CAS  Google Scholar 

  • Atkins H, Freedman M (2009) Immune ablation followed by autologous hematopoietic stem cell transplantation for the treatment of poor prognosis multiple sclerosis. Methods Mol Biol 549:231–246

    Article  PubMed  CAS  Google Scholar 

  • Barker JE (1994) Sl/Sld hematopoietic progenitors are deficient in situ. Exp Hematol 22:174–177

    PubMed  CAS  Google Scholar 

  • Barker JE (1997) Early transplantation to a normal microenvironment prevents the development of Steel hematopoietic stem cell defects. Exp Hematol 25:542–547

    PubMed  CAS  Google Scholar 

  • Bhatia M, Wang JC, Kapp U, Bonnet D, Dick JE (1997) Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. Proc Natl Acad Sci U S A 94:5320–5325

    Article  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 172:3893–3904

    PubMed  CAS  Google Scholar 

  • Bomberger C, Singh-Jairam M, Rodey G, Guerriero A, Yeager AM et al (1998) Lymphoid reconstitution after autologous PBSC transplantation with FACS-sorted CD34+ hematopoietic progenitors. Blood 91:2588–2600

    PubMed  CAS  Google Scholar 

  • Bonig H, Wundes A, Chang KH, Lucas S, Papayannopoulou T (2008) Increased numbers of circulating hematopoietic stem/progenitor cells are chronically maintained in patients treated with the CD49d blocking antibody natalizumab. Blood 111:3439–3441

    Article  PubMed  CAS  Google Scholar 

  • Brinkman DM, de Kleer IM, ten Cate R, van Rossum MA, Bekkering WP et al (2007) Autologous stem cell transplantation in children with severe progressive systemic or polyarticular juvenile idiopathic arthritis: long-term follow-up of a prospective clinical trial. Arthritis Rheum 56:2410–2421

    Article  PubMed  CAS  Google Scholar 

  • Burt RK, Burns W, Hess A (1995) Bone marrow transplantation for multiple sclerosis. Bone Marrow Transplant 16:1–6

    PubMed  CAS  Google Scholar 

  • Burt RK, Padilla J, Begolka WS, Canto MC, Miller SD (1998a) Effect of disease stage on clinical outcome after syngeneic bone marrow transplantation for relapsing experimental autoimmune encephalomyelitis. Blood 91:2609–2616

    CAS  Google Scholar 

  • Burt RK, Traynor AE, Cohen B, Karlin KH, Davis FA et al (1998b) T cell-depleted autologous hematopoietic stem cell transplantation for multiple sclerosis: report on the first three patients. Bone Marrow Transplant 21:537–541

    Article  CAS  Google Scholar 

  • Burt RK, Cohen BA, Russell E, Spero K, Joshi A et al (2003) Hematopoietic stem cell transplantation for progressive multiple sclerosis: failure of a total body irradiation-based conditioning regimen to prevent disease progression in patients with high disability scores. Blood 102:2373–2378

    Article  PubMed  CAS  Google Scholar 

  • Burt RK, Loh Y, Cohen B, Stefoski D, Balabanov R et al (2009) Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. Lancet Neurol 8:244–253

    Article  PubMed  CAS  Google Scholar 

  • Burt RK, Balabanov R, Voltarelli J, Barreira A, Burman J (2012) Autologous hematopoietic stem cell transplantation for multiple sclerosis–if confused or hesitant, remember: ‘treat with standard immune suppressive drugs and if no inflammation, no response’. Mult Scler 18:772–775

    Article  PubMed  Google Scholar 

  • Carreras E, Saiz A, Marin P, Martinez C, Rovira M 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 88:306–314

    PubMed  Google Scholar 

  • Cassiani-Ingoni R, Muraro PA, Magnus T, Reichert-Scrivner S, Schmidt J et al (2007) Disease progression after bone marrow transplantation in a model of multiple sclerosis is associated with chronic microglial and glial progenitor response. J Neuropathol Exp Neurol 66:637–649

    Article  PubMed  Google Scholar 

  • Chen B, Zhou M, Ouyang J, Zhou R, Xu J et al (2011) Long-term efficacy of autologous haematopoietic stem cell transplantation in multiple sclerosis at a single institution in China. Neurol Sci 33(4):881–886

    Article  PubMed  Google Scholar 

  • Civin CI, Strauss LC, Brovall C, Fackler MJ, Schwartz JF, Shaper JH (1984) Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. J Immunol 133:157–165

    PubMed  CAS  Google Scholar 

  • Comi G, Kappos L, Clanet M, Ebers G, Fassas A et al (2000) Guidelines for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for Blood and Marrow Transplantation and the European Charcot Foundation. BMT-MS Study Group. J Neurol 247:376–382

    Article  PubMed  CAS  Google Scholar 

  • Davenport RJ, Munday JR (2007) Alpha4-integrin antagonism—an effective approach for the treatment of inflammatory diseases? Drug Discov Today 12:569–576

    Article  PubMed  CAS  Google Scholar 

  • De Kleer I, Vastert B, Klein M, Teklenburg G, Arkesteijn G et al (2006) Autologous stem cell transplantation for autoimmunity induces immunologic self-tolerance by reprogramming autoreactive T cells and restoring the CD4+ CD25+ immune regulatory network. Blood 107:1696–1702

    Article  PubMed  CAS  Google Scholar 

  • Disanto G, Morahan JM, Barnett MH, Giovannoni G, Ramagopalan SV (2012a) The evidence for a role of B cells in multiple sclerosis. Neurology 78:823–832

    Article  CAS  Google Scholar 

  • Disanto G, Sandve GK, Berlanga-Taylor AJ, Morahan JM, Dobson R et al (2012b) Genomic regions associated with multiple sclerosis are active in B cells. PloS one 7:e32281

    Google Scholar 

  • Doulatov S, Notta F, Laurenti E, Dick JE (2012) Hematopoiesis: a human perspective. Cell stem. Cell 10:120–136

    CAS  Google Scholar 

  • Dubinsky AN, Burt RK, Martin R, Muraro PA (2010) T-cell clones persisting in the circulation after autologous hematopoietic SCT are undetectable in the peripheral CD34+ selected graft. Bone Marrow Transplant 45:325–331

    Article  PubMed  CAS  Google Scholar 

  • Eglitis MA, Mezey E (1997) Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci U S A 94:4080–4085

    Article  PubMed  CAS  Google Scholar 

  • Euler HH, Marmont AM, Bacigalupo A, Fastenrath S, Dreger P et al (1996) Early recurrence or persistence of autoimmune diseases after unmanipulated autologous stem cell transplantation. Blood 88:3621–3625

    PubMed  CAS  Google Scholar 

  • Fagius J, Lundgren J, Oberg G (2009) Early highly aggressive MS successfully treated by hematopoietic stem cell transplantation. Mult Scler 15:229–237

    Article  PubMed  CAS  Google Scholar 

  • Farge D, Labopin M, Tyndall A, Fassas A, Mancardi GL et al (2010) Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years’ experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases. Haematologica 95:284–292

    Article  PubMed  Google Scholar 

  • Fassas A, Anagnostopoulos A, Kazis A, Kapinas K, Sakellari I et al (1997) Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study. Bone Marrow Transplant 20:631–638

    Article  PubMed  CAS  Google Scholar 

  • Fassas A, Kimiskidis VK, Sakellari I, Kapinas K, Anagnostopoulos A et al (2011) Long-term results of stem cell transplantation for MS: a single-center experience. Neurology 76:1066–1070

    Article  PubMed  CAS  Google Scholar 

  • Freedman MS, Atkins HL, Arnold DL, Bar-Or A on behalf of the Canadian BMT group (2007) Immune ablation and autologous stem cell transplantation for aggressive multiple sclerosis: interim 5-year report. Mult Scler 13 (Suppl 2):22 (abstr)

    Google Scholar 

  • Fuchs E, Tumbar T, Guasch G (2004) Socializing with the neighbors: stem cells and their niche. Cell 116:769–778

    Article  PubMed  CAS  Google Scholar 

  • Gordon MY, Levicar N, Pai M, Bachellier P, Dimarakis I et al (2006) Characterization and clinical application of human CD34+ stem/progenitor cell populations mobilized into the blood by granulocyte colony-stimulating factor. Stem Cells 24:1822–1830

    Article  PubMed  Google Scholar 

  • Gratwohl A, Baldomero H, Aljurf M, Pasquini MC, Bouzas LF et al (2010) Hematopoietic stem cell transplantation: a global perspective. JAMA 303:1617–1624

    Article  PubMed  CAS  Google Scholar 

  • Griffith LM, Pavletic SZ, Tyndall A, Bredeson CN, Bowen JD et al (2005) Feasibility of allogeneic hematopoietic stem cell transplantation for autoimmune disease: position statement from a National Institute of Allergy and Infectious Diseases and National Cancer Institute-Sponsored International Workshop, Bethesda, MD, March 12 and 13, 2005. Biol Blood Marrow Transplant 11:862–870

    Article  PubMed  Google Scholar 

  • Gyurkocza B, Rezvani A, Storb RF (2010) Allogeneic hematopoietic cell transplantation: the state of the art. Expert Rev Hematol 3:285–299

    Article  PubMed  Google Scholar 

  • Hakim FT, Memon SA, Cepeda R, Jones EC, Chow CK et al (2005) Age-dependent incidence, time course, and consequences of thymic renewal in adults. J Clin Invest 115:930–939

    PubMed  CAS  Google Scholar 

  • Hamerschlak N, Rodrigues M, Moraes DA, Oliveira MC, Stracieri AB et al (2010) Brazilian experience with two conditioning regimens in patients with multiple sclerosis: BEAM/horse ATG and CY/rabbit ATG. Bone Marrow Transplant 45:239–248

    Article  PubMed  CAS  Google Scholar 

  • Harrer A, Wipfler P, Einhaeupl M, Pilz G, Oppermann K et al (2011) Natalizumab therapy decreases surface expression of both VLA-heterodimer subunits on peripheral blood mononuclear cells. J Neuroimmunol 234:148–154

    Article  PubMed  CAS  Google Scholar 

  • Harrer A, Pilz G, Einhaeupl M, Oppermann K, Hitzl W et al (2012) Lymphocyte subsets show different response patterns to in vivo bound natalizumab—a flow cytometric study on patients with multiple sclerosis. PloS one 7:e31784

    Google Scholar 

  • Herrmann MM, Gaertner S, Stadelmann C, van den BJ, Boscke R et al (2005) Tolerance induction by bone marrow transplantation in a multiple sclerosis model. Blood 106:1875–1883

    Article  PubMed  CAS  Google Scholar 

  • Ho J, Kurtz CC, Naganuma M, Ernst PB, Cominelli F, Rivera-Nieves J (2008) A CD8+/CD103high T cell subset regulates TNF-mediated chronic murine ileitis. J Immunol 180:2573–2580

    PubMed  CAS  Google Scholar 

  • Jansen M, Yang FC, Cancelas JA, Bailey JR, Williams DA (2005) Rac2-deficient hematopoietic stem cells show defective interaction with the hematopoietic microenvironment and long-term engraftment failure. Stem Cells 23:335–346

    Article  PubMed  CAS  Google Scholar 

  • Jing D, Oelschlaegel U, Ordemann R, Holig K, Ehninger G et al (2010) CD49d blockade by natalizumab in patients with multiple sclerosis affects steady-state hematopoiesis and mobilizes progenitors with a distinct phenotype and function. Bone Marrow Transplant 45:1489–1496

    Article  PubMed  CAS  Google Scholar 

  • Kamel-Reid S, Dick JE (1988) Engraftment of immune-deficient mice with human hematopoietic stem cells. Science 242:1706–1709

    Article  PubMed  CAS  Google Scholar 

  • Karussis DM, Slavin S, Ben-Nun A, Ovadia H, Vourka-Karussis U et al (1992a) Chronic-relapsing experimental autoimmune encephalomyelitis (CR-EAE): treatment and induction of tolerance, with high dose cyclophosphamide followed by syngeneic bone marrow transplantation. J Neuroimmunol 39:201–210

    Article  CAS  Google Scholar 

  • Karussis DM, Slavin S, Lehmann D, Mizrachi-Koll R, Abramsky O, Ben-Nun A (1992b) Prevention of experimental autoimmune encephalomyelitis and induction of tolerance with acute immunosuppression followed by syngeneic bone marrow transplantation. J Immunol 148:1693–1698

    CAS  Google Scholar 

  • Kiel MJ, Yilmaz OH, Iwashita T, Terhorst C, Morrison SJ (2005) SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121:1109–1121

    Article  PubMed  CAS  Google Scholar 

  • Kieper WC, Troy A, Burghardt JT, Ramsey C, Lee JY et al (2005) Recent immune status determines the source of antigens that drive homeostatic T cell expansion. J Immunol 174:3158–3163

    PubMed  CAS  Google Scholar 

  • Kimiskidis V, Sakellari I, Tsimourtou V, Kapina V, Papagiannopoulos S et al (2008) Autologous stem-cell transplantation in malignant multiple sclerosis: a case with a favorable long-term outcome. Mult Scler 14:278–283

    Article  PubMed  CAS  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 19:149–156

    Article  PubMed  CAS  Google Scholar 

  • Krasulova E, Trneny M, Kozak T, Vackova B, Pohlreich D et al (2010) High-dose immunoablation with autologous haematopoietic stem cell transplantation in aggressive multiple sclerosis: a single centre 10-year experience. Mult Scler 16:685–693

    Article  PubMed  Google Scholar 

  • Krumbholz M, Meinl I, Kumpfel T, Hohlfeld R, Meinl E (2008) Natalizumab disproportionately increases circulating pre-B and B cells in multiple sclerosis. Neurology 71:1350–1354

    Article  PubMed  CAS  Google Scholar 

  • Lapidot T, Petit I (2002) Current understanding of stem cell mobilization: the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Exp Hematol 30:973–81

    Article  PubMed  CAS  Google Scholar 

  • Lapidot T, Dar A, Kollet O (2005) How do stem cells find their way home? Blood 106:1901–1910

    Article  PubMed  CAS  Google Scholar 

  • Larochelle A, Savona M, Wiggins M, Anderson S, Ichwan B et al (2011) Human and rhesus macaque hematopoietic stem cells cannot be purified based only on SLAM family markers. Blood 117:1550–1554

    Article  PubMed  CAS  Google Scholar 

  • Li HW, Sykes M (2012) Emerging concepts in haematopoietic cell transplantation. Nat Rev Immunol 12:403–416

    Article  PubMed  CAS  Google Scholar 

  • Loh Y, Oyama Y, Statkute L, Quigley K, Yaung K et al (2007) Development of a secondary autoimmune disorder after hematopoietic stem cell transplantation for autoimmune diseases: role of conditioning regimen used. Blood 109:2643–2548

    Article  PubMed  CAS  Google Scholar 

  • Lu JQ, Storek J, Metz L, Yong VW, Stevens AM et al (2009) Continued disease activity in a patient with multiple sclerosis after allogeneic hematopoietic cell transplantation. Arch Neurol 66:116–120

    Article  PubMed  Google Scholar 

  • Lu JQ, Joseph JT, Nash RA, Storek J, Stevens AM et al (2010) Neuroinflammation and demyelination in multiple sclerosis after allogeneic hematopoietic stem cell transplantation. Arch Neurol 67:716–722

    Article  PubMed  Google Scholar 

  • Mallet VO, Mitchell C, Mezey E, Fabre M, Guidotti JE et al (2002) Bone marrow transplantation in mice leads to a minor population of hepatocytes that can be selectively amplified in vivo. Hepatology 35:799–804

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Mancardi GL, Sormani MP, Di Gioia M, Vuolo L, Gualandi F et al (2012) Autologous haematopoietic stem cell transplantation with an intermediate intensity conditioning regimen in multiple sclerosis: the Italian multi-centre experience. Mult Scler 18:835–842

    Article  PubMed  CAS  Google Scholar 

  • Marmont AM (1994) Immune ablation followed by allogeneic or autologous bone marrow transplantation: a new treatment for severe autoimmune diseases? Stem Cells 12:125–135

    Article  PubMed  CAS  Google Scholar 

  • Marmont AM (2004) Stem cell transplantation for autoimmune disorders. Coincidental autoimmune disease in patients transplanted for conventional indications. Best Pract Res Clin Haematol 17:223–232

    Article  PubMed  Google Scholar 

  • Mattoscio M, Nicholas R, Malik O, Dazzi F, Lee J, Waldman A et al (2012) Differential increase of circulating haematopoietic stem cells (HSC) following therapeutic alpha 4-integrin blockade in multiple sclerosis: correlation between HSC mobilization status and response to treatment (IN8-1.006). Neurology. April 22, 78(Meeting Abstracts 1):IN8-1.006

    Google Scholar 

  • Mattoscio M, Nicholas R, Malik O, Muraro P (2013) Circulating Hematopoietic Stem Cell Numbers during Natalizumab Treatment in Patients with Multiple Sclerosis: Association with Clinical and MRI Variables (P05.194). Neurology. February 14, 2013;80(Meeting Abstracts 1):P05.194

    Google Scholar 

  • Metz I, Lucchinetti CF, Openshaw H, Garcia-Merino A, Lassmann H et al (2007) Autologous haematopoietic stem cell transplantation fails to stop demyelination and neurodegeneration in multiple sclerosis. Brain 130:1254–1262

    Article  PubMed  Google Scholar 

  • Mezey E, Chandross KJ (2000) Bone marrow: a possible alternative source of cells in the adult nervous system. Eur J Pharmacol 405:297–302

    Article  PubMed  CAS  Google Scholar 

  • Mezey E, Chandross KJ, Harta G, Maki RA, McKercher SR (2000) Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 290:1779–1782

    Article  PubMed  CAS  Google Scholar 

  • Mezey E, Key S, Vogelsang G, Szalayova I, Lange GD, Crain B (2003) Transplanted bone marrow generates new neurons in human brains. Proc Natl Acad Sci U S A 100:1364–1369

    Article  PubMed  CAS  Google Scholar 

  • Mondria T, Lamers CH, te Boekhorst PA, Gratama JW, Hintzen RQ (2008) Bone-marrow transplantation fails to halt intrathecal lymphocyte activation in multiple sclerosis. J Neurol Neurosurg Psychiatry 79:1013–1015

    Article  PubMed  CAS  Google Scholar 

  • Muraro PA, Bielekova B (2007) Emerging therapies for multiple sclerosis. Neurother 4:676–692

    Article  CAS  Google Scholar 

  • Muraro PA, Leist T, Bielekova B, McFarland HF (2000) VLA-4/CD49d downregulated on primed T lymphocytes during interferon-b therapy in multiple sclerosis. J Neuroimmunol 111:186–194

    Google Scholar 

  • Muraro PA, Liberati L, Bonanni L, Pantalone A, Caporale CM et al (2004) Decreased integrin gene expression in patients with MS responding to interferon-beta treatment. J Neuroimmunol 150:123–131

    Article  PubMed  CAS  Google Scholar 

  • Muraro PA, Douek DC, Packer A, Chung K, Guenaga FJ et al (2005) Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J Exp Med 201:805–816

    Article  PubMed  CAS  Google Scholar 

  • Murray L, Chen B, Galy A, Chen S, Tushinski R et al (1995) Enrichment of human hematopoietic stem cell activity in the CD34+ Thy-1+Lin- subpopulation from mobilized peripheral blood. Blood 85:368–378

    PubMed  CAS  Google Scholar 

  • Nash RA, Bowen JD, McSweeney PA, Pavletic SZ, Maravilla KR et al (2003) High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis. Blood 102:2364–2372

    Article  PubMed  CAS  Google Scholar 

  • Nash R, Hutton GJ, Racke M, Popat U, Devine SM, Georges G, Griffith L, Muraro PA et al (2013) Treatment of severe relapsing-remitting multiple sclerosis with high-dose immunosuppressive therapy and autologous hematopoietic cell transplantation: 2-year follow-up results of the HALT MS clinical trial (Immune Tolerance Network: ITN033AI). BMT Tandem Meetings, 13 Feb 2013–17 Feb 2013. Biol Blood Marrow Transplant 19(2):S 129

    Google Scholar 

  • Ni XS, Ouyang J, Zhu WH, Wang C, Chen B (2006) Autologous hematopoietic stem cell transplantation for progressive multiple sclerosis: report of efficacy and safety at three yr of follow up in 21 patients. Clin Transplant 20:485–489

    Article  PubMed  Google Scholar 

  • O’Gorman WE, Dooms H, Thorne SH, Kuswanto WF, Simonds EF et al (2009) The initial phase of an immune response functions to activate regulatory T cells. J Immunol 183:332–339

    Article  PubMed  CAS  Google Scholar 

  • Osawa M, Hanada K, Hamada H, Nakauchi H (1996) Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science 273:242–245

    Article  PubMed  CAS  Google Scholar 

  • Papayannopoulou T, Nakamoto B (1993) Peripheralization of hemopoietic progenitors in primates treated with anti-VLA4 integrin. Proc Natl Acad Sci U S A 90:9374–9378

    Article  PubMed  CAS  Google Scholar 

  • Papayannopoulou T, Priestley GV, Nakamoto B, Zafiropoulos V, Scott LM (2001) Molecular pathways in bone marrow homing: dominant role of alpha(4)beta(1) over beta(2)-integrins and selectins. Blood 98:2403–2411

    Article  PubMed  CAS  Google Scholar 

  • Pike BL, Robinson WA (1970) Human bone marrow colony growth in agar-gel. J Cell Physiol 76:77–84

    Article  PubMed  CAS  Google Scholar 

  • Polman CH, O’Connor PW, Havrdova E, Hutchinson M, Kappos L et al (2006) A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354:899–910

    Article  PubMed  CAS  Google Scholar 

  • Radbruch A, Muehlinghaus G, Luger EO, Inamine A, Smith KG et al (2006) Competence and competition: the challenge of becoming a long-lived plasma cell. Nat Rev Immunol 6:741–750

    Article  PubMed  CAS  Google Scholar 

  • Randall TD, Weissman IL (1997) Phenotypic and functional changes induced at the clonal level in hematopoietic stem cells after 5-fluorouracil treatment. Blood 89:3596–3606

    PubMed  CAS  Google Scholar 

  • Rose DM, Alon R, Ginsberg MH (2007) Integrin modulation and signaling in leukocyte adhesion and migration. Immunol Rev 218:126–134

    Article  PubMed  CAS  Google Scholar 

  • Rutella S, Rumi C, Laurenti L, Pierelli L, Sora F et al (2000) Immune reconstitution after transplantation of autologous peripheral CD34+ cells: analysis of predictive factors and comparison with unselected progenitor transplants. Br J Haematol 108:105–115

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Saccardi R, Kozak T, Bocelli-Tyndall C, Fassas A, Kazis A, Havrdova E, Carreras E, Saiz A, Löwenberg B, te Boekhorst PA, Gualandio F, Openshaw H, Longo G, Pagliai F, Massacesi L, Deconink E, Ouyang J, Nagore FJ, Besalduch J, Lisukov IA, Bonini A, Merelli E, Slavino S, Gratwohl A, Passweg J, Tyndall A, Steck AJ, Andolina M, Capobianco M, Martin JL, Lugaresi A, Meucci G, Sáez RA, Clark RE, Fernandez MN, Fouillard L, Herstenstein B, Koza V, Cocco E, Baurmann H, Mancardi GL, Autoimmune Diseases Working Party of EBMT (2006) Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database. Mult Scler 12(6):814–823

    Google Scholar 

  • Saccardi R, Freedman M, Sormani M, Atkins H, Farge D et al (2012) A prospective, randomized, controlled trial of autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: a position paper. Mult Scler 18:825–834

    Article  PubMed  CAS  Google Scholar 

  • Saiz A, Carreras E, Berenguer J, Yague J, Martinez C et al (2001) MRI and CSF oligoclonal bands after autologous hematopoietic stem cell transplantation in MS. Neurology 56:1084–1089

    Article  PubMed  CAS  Google Scholar 

  • Saiz A, Blanco Y, Berenguer J, Gomez-Choco M, Carreras E et al (2008) Clinical outcome 6 years after autologous hematopoietic stem cell transplantation in multiple sclerosis. Neurologia 23:405–407

    PubMed  CAS  Google Scholar 

  • Samijn JP, te Boekhorst PA, Mondria T, van Doorn PA, Flach HZ et al (2006) Intense T cell depletion followed by autologous bone marrow transplantation for severe multiple sclerosis. J Neurol Neurosurg Psychiatry 77:46–50

    Article  PubMed  CAS  Google Scholar 

  • Sangalli F, Moiola L, Bucello S, Annovazzi P, Rizzo A et al (2011) Efficacy and tolerability of natalizumab in relapsing-remitting multiple sclerosis patients: a post-marketing observational study. Neurol Sci 31(Suppl 3):299–302

    Article  PubMed  Google Scholar 

  • Saure C, Warnke C, Zohren F, Schroeder T, Bruns I et al (2011) Natalizumab and impedance of the homing of CD34+ hematopoietic progenitors. Arch Neurol 68:1428–1431

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Shevchenko YL, Novik AA, Kuznetsov AN, Afanasiev BV, Lisukov IA et al (2008) High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis. Exp Hematol 36:922–928

    Article  PubMed  CAS  Google Scholar 

  • Shevchenko JL, Kuznetsov AN, Ionova TI, Melnichenko VY, Fedorenko DA et al (2012) Autologous haematopoietic stem cell transplantation with reduced intensity conditioning in multiple sclerosis. Exp Hematol 40(11):892–898

    Article  PubMed  Google Scholar 

  • Sigurjonsson OE, Perreault MC, Egeland T, Glover JC (2005) Adult human hematopoietic stem cells produce neurons efficiently in the regenerating chicken embryo spinal cord. Proc Natl Acad Sci U S A 102:5227–5232

    Article  PubMed  CAS  Google Scholar 

  • Sitnicka E, Buza-Vidas N, Larsson S, Nygren JM, Liuba K, Jacobsen SE (2003) Human CD34+ hematopoietic stem cells capable of multilineage engrafting NOD/SCID mice express flt3: distinct flt3 and c-kit expression and response patterns on mouse and candidate human hematopoietic stem cells. Blood 102:881–886

    Article  PubMed  CAS  Google Scholar 

  • Snowden JA, Saccardi R, Allez M, Ardizzone S, Arnold R et al (2012) Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 47:770–790

    Article  PubMed  CAS  Google Scholar 

  • Storek J, Zhao Z, Liu Y, Nash R, McSweeney P, Maloney DG (2008) Early recovery of CD4T cell receptor diversity after “lymphoablative” conditioning and autologous CD34 cell transplantation. Biol Blood Marrow Transplant 14:1373–1379

    Article  PubMed  CAS  Google Scholar 

  • Stuve O (2008) The effects of natalizumab on the innate and adaptive immune system in the central nervous system. J Neurol Sci 274:39–41

    Article  PubMed  CAS  Google Scholar 

  • Stuve O, Cravens PD, Frohman EM, Phillips JT, Remington GM et al (2009) Immunologic, clinical, and radiologic status 14 months after cessation of natalizumab therapy. Neurology 72:396–401

    Article  PubMed  CAS  Google Scholar 

  • Su L, Xu J, Ji BX, Wan SG, Lu CY et al (2006) Autologous peripheral blood stem cell transplantation for severe multiple sclerosis. Int J Hematol 84:276–281

    Article  PubMed  Google Scholar 

  • Sun W, Popat U, Hutton G, Zang YC, Krance R et al (2004) Characteristics of T-cell receptor repertoire and myelin-reactive T cells reconstituted from autologous haematopoietic stem-cell grafts in multiple sclerosis. Brain 127:996–1008

    Article  PubMed  Google Scholar 

  • Sutherland HJ, Eaves CJ, Eaves AC, Dragowska W, Lansdorp PM (1989) Characterization and partial purification of human marrow cells capable of initiating long-term hematopoiesis in vitro. Blood 74:1563–1570

    PubMed  CAS  Google Scholar 

  • Till JE, Mc CE (1961) A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res 14:213–222

    Article  PubMed  CAS  Google Scholar 

  • Uss E, Rowshani AT, Hooibrink B, Lardy NM, van Lier RA, ten Berge IJ (2006) CD103 is a marker for alloantigen-induced regulatory CD8+ T cells. J Immunol 177:2775–2783

    PubMed  CAS  Google Scholar 

  • van Gelder M, van Bekkum DW (1996) Effective treatment of relapsing experimental autoimmune encephalomyelitis with pseudoautologous bone marrow transplantation. Bone Marrow Transplant 18:1029–1034

    PubMed  Google Scholar 

  • van Gelder M, Kinwel-Bohre EP, van Bekkum DW(1993) Treatment of experimental allergic encephalomyelitis in rats with total body irradiation and syngeneic BMT. Bone Marrow Transplant 11:233–241

    PubMed  Google Scholar 

  • Van Wijmeersch B, Sprangers B, Rutgeerts O, Lenaerts C, Landuyt W et al (2007) Allogeneic bone marrow transplantation in models of experimental autoimmune encephalomyelitis: evidence for a graft-versus-autoimmunity effect. Biol Blood Marrow Transplant 13:627–637

    Article  PubMed  CAS  Google Scholar 

  • Venken K, Hellings N, Thewissen M, Somers V, Hensen K et al (2008) Compromised CD4+ CD25(high) regulatory T-cell function in patients with relapsing-remitting multiple sclerosis is correlated with a reduced frequency of FOXP3-positive cells and reduced FOXP3 expression at the single-cell level. Immunology 123:79–89

    Article  PubMed  CAS  Google Scholar 

  • Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA (2004) Loss of functional suppression by CD4+ CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 199:971–979

    Article  PubMed  CAS  Google Scholar 

  • Warnke C, Smolianov V, Dehmel T, Andree M, Hengel H et al (2011) CD34+ progenitor cells mobilized by natalizumab are not a relevant reservoir for JC virus. Mult Scler 17:151–156

    Article  PubMed  Google Scholar 

  • Weissman IL (2000) Stem cells: units of development, units of regeneration, and units in evolution. Cell 100:157–168

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Wilson A, Oser GM, Jaworski M, Blanco-Bose WE, Laurenti E et al (2007) Dormant and self-renewing hematopoietic stem cells and their niches. Ann N Y Acad Sci 1106:64–75

    Google Scholar 

  • Wilson A, Laurenti E, Oser G, van der Wath RC, Blanco-Bose W et al (2008) Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair. Cell 135:1118–1129

    Article  PubMed  CAS  Google Scholar 

  • Wilson A, Laurenti E, Trumpp A (2009) Balancing dormant and self-renewing hematopoietic stem cells. Curr Opin Genet Dev 19:461–468

    Article  PubMed  CAS  Google Scholar 

  • Winstead CJ, Fraser JM, Khoruts A (2008) Regulatory CD4+CD25+Foxp3+ T cells selectively inhibit the spontaneous form of lymphopenia-induced proliferation of naive T cells. J Immunol 180:7305–7317

    PubMed  CAS  Google Scholar 

  • Winstead CJ, Reilly CS, Moon JJ, Jenkins MK, Hamilton SE et al (2010) CD4+CD25+Foxp3+ regulatory T cells optimize diversity of the conventional T cell repertoire during reconstitution from lymphopenia. J Immunol 184:4749–4760

    Article  PubMed  CAS  Google Scholar 

  • Zand MS, Vo T, Huggins J, Felgar R, Liesveld J et al (2005) Polyclonal rabbit antithymocyte globulin triggers B-cell and plasma cell apoptosis by multiple pathways. Transplantation 79:1507–1515

    Article  PubMed  CAS  Google Scholar 

  • Zhang H, Chua KS, Guimond M, Kapoor V, Brown MV et al (2005) Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells. Nat Med 11:1238–1243

    Article  PubMed  CAS  Google Scholar 

  • Zhang J, Niu C, Ye L, Huang H, He X et al (2003) Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425:836–841

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, Bertucci AM, Ramsey-Goldman R, Burt RK, Datta SK (2009) Regulatory T cell (Treg) subsets return in patients with refractory lupus following stem cell transplantation, and TGF-beta-producing CD8+ Treg cells are associated with immunological remission of lupus. J Immunol 183:6346–6358

    Article  PubMed  CAS  Google Scholar 

  • Zohren F, Toutzaris D, Klarner V, Hartung HP, Kieseier B, Haas R (2008) The monoclonal anti-VLA-4 antibody natalizumab mobilizes CD34+ hematopoietic progenitor cells in humans. Blood 111:3893–3895

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by grants from the UK MS Society (Ref. 938/10) and the Italian MS Society (FISM; ref. no. 2010/R/24; and ref. no. 2010/B/10).

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Authors and Affiliations

  1. Division of Brain Sciences, Faculty of Medicine, Imperial College London, Building 560/Burlington Danes, Room E415, 160 Du Cane Road, W12 0NN, London, UK

    Sofia Abrahamsson, Miriam Mattoscio & Paolo A. Muraro

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  1. Sofia Abrahamsson
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  2. Miriam Mattoscio
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  3. Paolo A. Muraro
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Correspondence to Paolo A. Muraro .

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  1. National Institute of Neuroscience, National Center of Neurology and Psychia, Tokyo, Japan

    Takashi Yamamura

  2. Clinical Neurology, University of Nottingham, Nottingham, United Kingdom

    Bruno Gran

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Abrahamsson, S., Mattoscio, M., Muraro, P. (2013). Haematopoietic Stem Cells for the Treatment of MS. In: Yamamura, T., Gran, B. (eds) Multiple Sclerosis Immunology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7953-6_19

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