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Review

Progress and prospects for the use and the understanding of the mode of action of autologous hematopoietic stem cell transplantation in the treatment of multiple sclerosis

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Pages 611-622 | Received 18 Nov 2016, Accepted 16 Feb 2017, Published online: 20 Mar 2017

References

  • Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Publish Group. 2015;15(9):545–558. DOI:10.1038/nri3871
  • Dutta R, Trapp BD. Mechanisms of neuronal dysfunction and degeneration in multiple sclerosis. Prog Neurobiol. 2011;93(1):1–12. DOI:10.1016/j.pneurobio.2010.09.005
  • Scolding N, Barnes D, Cader S, et al. Association of British Neurologists: revised (2015). Guidelines for prescribing disease-modifying treatments in multiple sclerosis. Pract Neurol. 2015;15(4):273–279. DOI:10.1136/practneurol-2015-001139.
  • Fassas A, Anagnostopoulos A, Kazis A, et al. Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study. Bone Marrow Transplant. 1997;20(8):631–638.
  • Snowden JA, Saccardi R, Allez M, et al. Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2012;47(6):770–790. DOI:10.1038/bmt.2011.185
  • Burt RK, Slavin S, Burns WH, et al. Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: getting closer to a cure? Blood. 2002;99(3):768–784. DOI:10.1182/blood.V99.3.768
  • Burt RK, Padilla J, Begolka WS, et al. Effect of disease stage on clinical outcome after syngeneic bone marrow transplantation for relapsing experimental autoimmune encephalomyelitis. Blood. 1998;91(7):2609–2616. DOI:10.1111/j.1600-065X.1981.tb00337.x
  • van Bekkum DW. Stem cell transplantation in experimental models of autoimmune disease. J Clin Immunol. 2000;20(1):10–16. DOI:10.1023/A:1006682225181
  • Karussis DM, Vourka-Karussis U, Lehmann D, et al. Prevention and reversal of adoptively transferred, chronic relapsing experimental autoimmune encephalomyelitis with a single high dose cytoreductive treatment followed by syngeneic bone marrow transplantation. J Clin Invest. 1993;92(2):765–772. DOI:10.1172/JCI116648
  • Karussis DM, Slavin S, Ben-Nun A, et al. Chronic-relapsing experimental autoimmune encephalomyelitis (CR-EAE): treatment and induction of tolerance, with high dose cyclophosphamide followed by syngeneic bone marrow transplantation. J Neuroimmunol. 1992;39(3):201–210. DOI:10.1016/0165-5728(92)90254-I
  • Karussis DM, Slavin S, Lehmann D, et al. Prevention of experimental autoimmune encephalomyelitis and induction of tolerance with acute immunosuppression followed by syngeneic bone marrow transplantation. J Immunol. 1992;148(6):1693–1698.
  • van Gelder M, Kinwel-Bohre EP, van Bekkum DW. Treatment of experimental allergic encephalomyelitis in rats with total body irradiation and syngeneic BMT. Bone Marrow Transplant. 1993;11(3):233–241.
  • Cassiani-Ingoni R, Muraro PA, Magnus T, et al. 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. 2007;66(7):637–649. DOI:10.1097/nen.0b013e318093f3ef
  • van Gelder M, Van Bekkum DW. Effective treatment of relapsing experimental autoimmune encephalomyelitis with pseudoautologous bone marrow transplantation. Bone Marrow Transplant. 1996;18(6):1029–1034.
  • van Bekkum DW. Experimental basis of hematopoietic stem cell transplantation for treatment of autoimmune diseases. J Leukoc Biol. 2002;72(4):609–620. DOI:10.1016/S0065-2776(08)60753-1
  • Chan J, Ban EJ, Chun KH, et al. Transplantation of bone marrow transduced to express self-antigen establishes deletional tolerance and permanently remits autoimmune disease. J Immunol. 2008;181(11):7571–7580. DOI:10.4049/jimmunol.181.11.7571
  • Brocker T, Riedinger M, Karjalainen K. Targeted expression of major histocompatibility complex (MHC) class II molecules demonstrates that dendritic cells can induce negative but not positive selection of thymocytes in vivo. J Exp Med. 1997;185(3):541–550. DOI:10.1084/jem.185.3.541
  • Mancardi GL, Sormani MP, Gualandi F, et al. Autologous hematopoietic stem cell transplantation in multiple sclerosis: a phase II trial. Neurology. 2015;84(10):981–988. DOI:10.1212/WNL.0000000000001329
  • Currò D, Mancardi G. Autologous hematopoietic stem cell transplantation in multiple sclerosis: 20 years of experience. Neurol Sci. 2016;37(6):857–865. DOI:10.1007/s10072-016-2564-3
  • Saccardi R, Freedman M, Sormani M, et al. A prospective, randomized, controlled trial of autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: a position paper. Mult Scler. 2012;18(6):825–834. DOI:10.1177/1352458512438454
  • Nash RA, Hutton GJ, Racke MK, et al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis (HALT-MS). JAMA Neurol. 2015;72(2):159–169. DOI:10.1001/jamaneurol.2014.3780
  • Burman J, Iacobaeus E, Svenningsson A, et al. Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience. J Neurol Neurosurg Psychiatr. 2014;85(10):1116–1121. DOI:10.1136/jnnp-2013-307207
  • Burt RK, Balabanov R, Han X, et al. Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsing-remitting multiple sclerosis. JAMA. 2015;313(3):275–284. DOI:10.1001/jama.2014.17986
  • Sormani MP, Muraro P. Updated views on autologous hematopoietic stem cell transplantation for treatment of multiple sclerosis. Expert Rev Neurother. 2016;16(5):469–470. DOI:10.1586/14737175.2016.1158648
  • Coles AJ, Twyman CL, Arnold DL, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. The Lancet. 2012;380(9856):1829–1839. DOI:10.1016/S0140-6736(12)61768-1
  • Butzkueven H, Kappos L, Pellegrini F, et al. Efficacy and safety of natalizumab in multiple sclerosis: interim observational program results. J Neurol Neurosurg Psychiatr. 2014;85(11):jnnp–2013–306936–1197. DOI:10.1136/jnnp-2013-306936
  • Atkins HL, Bowman M, Allan D, et al. Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial. The Lancet. 2016;388(10044):576–585. DOI:10.1016/S0140-6736(16)30169-6
  • Mancardi G, Sormani M, Di Gioia M, et al. Autologous haematopoietic stem cell transplantation with an intermediate intensity conditioning regimen in multiple sclerosis: the Italian multi-centre experience. Mult Scler. 2012;18(6):835–842. DOI:10.1177/1352458511429320
  • Krasulova E, Trneny M, Kozak T, et al. High-dose immunoablation with autologous haematopoietic stem cell transplantation in aggressive multiple sclerosis: a single centre 10-year experience. Mult Scler. 2010;16(6):685–693. DOI:10.1177/1352458510364538
  • Fassas A, Kimiskidis VK, Sakellari I, et al. Long-term results of stem cell transplantation for MS: a single-center experience. Neurology. 2011;76(12):1066–1070. DOI:10.1212/WNL.0b013e318211c537
  • Scalfari A, Lederer C, Daumer M, et al. The relationship of age with the clinical phenotype in multiple sclerosis. Mult Scler. 2016;22(13):1750–1758. DOI:10.1177/1352458516630396
  • Burman J, Fransson M, Tötterman TH, et al. T-cell responses after haematopoietic stem cell transplantation for aggressive relapsing-remitting multiple sclerosis. Immunology. 2013;140(2):211–219. DOI:10.1111/imm.12129
  • Fagius J, Lundgren J, Oberg G. Early highly aggressive MS successfully treated by hematopoietic stem cell transplantation. Mult Scler. 2008;15(2):229–237. DOI:10.1177/1352458508096875
  • Chen B, Zhou M, Ouyang J, et al. Long-term efficacy of autologous haematopoietic stem cell transplantation in multiple sclerosis at a single institution in China. Neurol Sci. 2011;33(4):881–886. DOI:10.1007/s10072-011-0859-y
  • Sousa A, De PA, Malmegrim KCR, et al. Autologous haematopoietic stem cell transplantation reduces abnormalities in the expression of immune genes in multiple sclerosis. Clin Sci. 2015;128(2):111–120. DOI:10.1042/CS20140095
  • Uccelli A, Laroni A, Freedman MS. Mesenchymal stem cells for the treatment of multiple sclerosis and other neurological diseases. Lancet Neurol. 2011;10(7):649–656. DOI:10.1016/S1474-4422(11)70121-1
  • Samijn JPA, Boekhorst te PAW, Mondria T, et al. Intense T cell depletion followed by autologous bone marrow transplantation for severe multiple sclerosis. J Neurol Neurosurg Psychiatr. 2006;77(1):46–50. DOI:10.1136/jnnp.2005.063883
  • Openshaw H, Lund BT, Kashyap A, et al. Peripheral blood stem cell transplantation in multiple sclerosis with busulfan and cyclophosphamide conditioning: report of toxicity and immunological monitoring. Biol Blood Marrow Transplant. 2000;6(5):563–575. DOI:10.1016/S1083-8791(00)70066-8
  • Nash RA, Bowen JD, McSweeney PA, et al. High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis. Blood. 2003;102(7):2364–2372. DOI:10.1182/blood-2002-12-3908
  • Mancardi G, Saccardi R. Autologous haematopoietic stem-cell transplantation in multiple sclerosis. Lancet Neurol. 2008;7(7):626–636. DOI:10.1016/S1474-4422(08)70138-8
  • Reston JT, Uhl S, Treadwell JR, et al. Autologous hematopoietic cell transplantation for multiple sclerosis: a systematic review. Mult Scler. 2011;17(2):204–213. DOI:10.1177/1352458510383609
  • Hamerschlak N, Rodrigues M, Moraes DA, et al. Brazilian experience with two conditioning regimens in patients with multiple sclerosis: BEAMsol;horse ATG and CY/rabbit ATG. Bone Marrow Transplant. 2009;45(2):239–248. DOI:10.1038/bmt.2009.127
  • Currò D, Vuolo L, Gualandi F, et al. Low intensity lympho-ablative regimen followed by autologous hematopoietic stem cell transplantation in severe forms of multiple sclerosis: a MRI-based clinical study. Mult Scler. 2015;21(11):1352458514564484. DOI:10.1177/1352458514564484
  • Muraro PA, Douek DC, Packer A, et al. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J Exp Med. 2005;201(5):805–816. DOI:10.1084/jem.20041679
  • Abrahamsson SV, Angelini DF, Dubinsky AN, et al. Non-myeloablative autologous haematopoietic stem cell transplantation expands regulatory cells and depletes IL-17 producing mucosal-associated invariant T cells in multiple sclerosis. Brain. 2013;136(9):2888–2903. DOI:10.1093/brain/awt182
  • Shevchenko JL, Kuznetsov AN, Ionova TI, et al. Autologous hematopoietic stem cell transplantation with reduced-intensity conditioning in multiple sclerosis. Exp Hematol. 2012;40(11):892–898. DOI:10.1016/j.exphem.2012.07.003
  • Shevchenko JL, Kuznetsov AN, Ionova TI, et al. Long-term outcomes of autologous hematopoietic stem cell transplantation with reduced-intensity conditioning in multiple sclerosis: physician’s and patient’s perspectives. Ann Hematol. 2015;94(7):1149–1157. DOI:10.1007/s00277-015-2337-8
  • Farge D, Labopin M, Tyndall A, et al. 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. 2010;95(2):284–292. DOI:10.3324/haematol.2009.013458
  • Wood WA, Krishnamurthy J, Mitin N, et al. Chemotherapy and stem cell transplantation increase p16INK4a expression, a biomarker of T-cell aging. Ebiom. 2016 October 1–12. DOI:10.1016/j.ebiom.2016.08.029
  • Arruda LCM, De Azevedo JTC, de Oliveira GLV, et al. Immunological correlates of favorable long-term clinical outcome in multiple sclerosis patients after autologous hematopoietic stem cell transplantation. Clin Immunol. 2016;169(C):47–57. DOI:10.1016/j.clim.2016.06.005
  • Darlington PJ, Touil T, Doucet J-S, et al. Diminished Th17 (not Th1) responses underlie multiple sclerosis disease abrogation after hematopoietic stem cell transplantation. Ann Neurol. 2013;73(3):341–354. DOI:10.1002/ana.23784
  • Arruda LCM, Lorenzi JCC, Sousa APA, et al. Autologous hematopoietic SCT normalizes miR-16, −155 and −142-3p expression in multiple sclerosis patients. Bone Marrow Transplant. 2014 December 1–10. DOI:10.1038/bmt.2014.277
  • Muraro PA, Robins H, Malhotra S, et al. T cell repertoire following autologous stem cell transplantation for multiple sclerosis. J Clin Invest. 2014;124(3):1168–1172. DOI:10.1172/JCI71691
  • Farge D, Henegar C, Carmagnat M, et al. Analysis of immune reconstitution after autologous bone marrow transplantation in systemic sclerosis. Arthritis Rheumatol. 2005;52(5):1555–1563. DOI:10.1002/art.21036
  • Alexander T, Thiel A, Rosen O, et al. 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. 2009;113(1):214–223. DOI:10.1182/blood-2008-07-168286
  • Alexander T, Arnold R, Hiepe F, etal. Resetting the immune system with immunoablation and autologous haematopoietic stem cell transplantation in autoimmune diseases. Clin Exp Rheumatol. 2016;34(4):S53–S57.
  • Venken K, Hellings N, Thewissen M, et al. Compromised CD4+ CD25high 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. 2008;123(1):79–89. DOI:10.1111/j.1365-2567.2007.02690.x
  • Laplaud DA, Ruiz C, Wiertlewski S, et al. Blood T‐cell receptor β chain transcriptome in multiple sclerosis. Characterization of the T cells with altered CDR3 length distribution. Brain. 2004;127(5):981–995. DOI:10.1093/brain/awh119
  • Sun W. Characteristics of T-cell receptor repertoire and myelin-reactive T cells reconstituted from autologous haematopoietic stem-cell grafts in multiple sclerosis. Brain. 2004;127(5):996–1008. DOI:10.1093/brain/awh117
  • Lopez M, Clarkson MR, Albin M, et al. A novel mechanism of action for anti-thymocyte globulin: induction of CD4+CD25+Foxp3+ regulatory T cells. Jasn. 2006;17(10):2844–2853. DOI:10.1681/ASN.2006050422
  • Autran B, Leblond V, Sadat-Sowti B, et al. A soluble factor released by CD8+CD57+ lymphocytes from bone marrow transplanted patients inhibits cell-mediated cytolysis. Blood. 1991;77(10):2237–2241.
  • Mollet L, Sadat-Sowti B, Duntze J, et al. CD8hi+CD57+ T lymphocytes are enriched in antigen-specific T cells capable of down-modulating cytotoxic activity. Int Immunol. 1998;10(3):311–323.
  • Sadat-Sowti B, Debre P, Mollet L, et al. An inhibitor of cytotoxic functions produced by CD8+CD57+ T lymphocytes from patients suffering from AIDS and immunosuppressed bone marrow recipients. Eur J Immunol. 1994;24(11):2882–2888. DOI:10.1002/eji.1830241145
  • O’Gorman WE, Dooms H, Thorne SH, et al. The initial phase of an immune response functions to activate regulatory T cells. J Immunol. 2009;183(1):332–339. DOI:10.4049/jimmunol.0900691
  • Kebir H, Ifergan I, Alvarez JI, et al. Preferential recruitment of interferon‐γ–expressing TH17 cells in multiple sclerosis. Ann Neurol. 2009;66(3):390–402. DOI:10.1002/ana.21748
  • Reboldi A, Coisne C, Baumjohann D, et al. C-C chemokine receptor 6–regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE. Nat Immunol. 2009;10(5):514–523. DOI:10.1038/ni.1716
  • Annibali V, Ristori G, Angelini DF, et al. CD161highCD8+T cells bear pathogenetic potential in multiple sclerosis. Brain. 2011;134(2):542–554. DOI:10.1093/brain/awq354
  • Baltimore D, Boldin MP, O’Connell RM, et al. MicroRNAs: new regulators of immune cell development and function. Nat Immunol. 2008;9(8):839–845. DOI:10.1038/ni.f.209
  • Paraboschi EM, Soldà G, Gemmati D, et al. Genetic association and altered gene expression of mir-155 in multiple sclerosis patients. Int J Mol Sci. 2011;12(12):8695–8712. DOI:10.3390/ijms12128695
  • Murugaiyan G, Beynon V, Mittal A, et al. Silencing microRNA-155 ameliorates experimental autoimmune encephalomyelitis. J Immunol. 2011;187(5):2213–2221. DOI:10.4049/jimmunol.1003952
  • Waschbisch A, Atiya M, Linker RA, et al. Glatiramer acetate treatment normalizes deregulated microRNA expression in relapsing remitting multiple sclerosis. Kleinschnitz C, ed. PloS ONE. 2011;6(9):e24604. DOI:10.1371/journal.pone.0024604
  • Keller A, Leidinger P, Steinmeyer F, et al. Comprehensive analysis of microRNA profiles in multiple sclerosis including next-generation sequencing. Mult Scler. 2014;20(3):295–303. DOI:10.1177/1352458513496343
  • Feng X, Petraglia AL, Chen M, et al. Low expression of interferon-stimulated genes in active multiple sclerosis is linked to subnormal phosphorylation of STAT1. J Neuroimmunol. 2002;129(1–2):205–215.
  • Liu X, Robinson SN, Setoyama T, et al. FOXP3 is a direct target of miR15a/16 in umbilical cord blood regulatory T cells. Bone Marrow Transplant. 2014;49(6):793–799. DOI:10.1038/bmt.2014.57
  • Huang B, Zhao J, Lei Z, et al. miR-142-3p restricts cAMP production in CD4+CD25- T cells and CD4+CD25+ TREG cells by targeting AC9 mRNA. EMBO Rep. 2009;10(2):180–185. DOI:10.1038/embor.2008.224
  • Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–1034. DOI:10.1084/jem.192.7.1027
  • Trabattoni D, Saresella M, Pacei M, et al. Costimulatory pathways in multiple sclerosis: distinctive expression of PD-1 and PD-L1 in patients with different patterns of disease. J Immunol. 2009;183(8):4984–4993. DOI:10.4049/jimmunol.0901038
  • Francisco LM, Salinas VH, Brown KE, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med. 2009;206(13):3015–3029. DOI:10.1084/jem.20090847
  • Sharpe AH, Wherry EJ, Ahmed R, et al. The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat Immunol. 2007;8(3):239–245. DOI:10.1038/ni1443
  • Carter LL, Leach MW, Azoitei ML, et al. PD-1/PD-L1, but not PD-1/PD-L2, interactions regulate the severity of experimental autoimmune encephalomyelitis. J Neuroimmunol. 2007;182(1–2):124–134. DOI:10.1016/j.jneuroim.2006.10.006
  • Zhu B, Guleria I, Khosroshahi A, et al. Differential role of programmed death-ligand 1 and programmed death-ligand 2 in regulating the susceptibility and chronic progression of experimental autoimmune encephalomyelitis. J Immunol. 2006;176(6):3480–3489.
  • Salama AD, Chitnis T, Imitola J, et al. Critical role of the programmed death-1 (PD-1) pathway in regulation of experimental autoimmune encephalomyelitis. J Exp Med. 2003;198(1):71–78. DOI:10.1084/jem.20022119
  • Kroner A, Mehling M, Hemmer B, et al. A PD‐1 polymorphism is associated with disease progression in multiple sclerosis. Ann Neurol. 2005;58(1):50–57. DOI:10.1002/ana.20514
  • McKinney EF, Lee JC, Jayne DRW, et al. T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection. Nature. 2015;523(7562):612–616. DOI:10.1038/nature14468

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