Archives of Neuroscience

Published by: Kowsar

Stem Cell Therapy ‒ Approach for Multiple Sclerosis Treatment

Masoud Soleimani 1 , 2 , Hamid Reza Aghayan 1 , 3 , Parisa Goodarzi 1 , Majid Farshdousti Hagh 4 , Abdolreza Ardeshiry Lajimi 5 , Najmaldin Saki 6 , Fereshteh Mohamadi Jahani 1 , Abbas Norouzi Javidan 1 and Babak Arjmand 7 , *
Authors Information
1 Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences, Tehran, IR Iran
2 Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IR Iran
3 Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, IR Iran
4 Division of Laboratory Hematology and Blood Banking, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, IR Iran
5 Young Researchers Club, Science and Research Branch, Islamic Azad University, Tehran, IR Iran
6 Research Center of Thalassemia & Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
7 Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, IR Iran
Article information
  • Archives of Neuroscience: January 01, 2016, 3 (1); e21564
  • Published Online: January 30, 2016
  • Article Type: Review Article
  • Received: June 29, 2014
  • Revised: December 1, 2014
  • Accepted: May 6, 2015
  • DOI: 10.5812/archneurosci.21564

To Cite: Soleimani M, Aghayan H R, Goodarzi P, Farshdousti Hagh M, Ardeshiry Lajimi A, et al. Stem Cell Therapy ‒ Approach for Multiple Sclerosis Treatment, Arch Neurosci. 2016 ; 3(1):e21564. doi: 10.5812/archneurosci.21564.

Copyright © 2016, Tehran University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Context
2. Evidence Acquisition
3. Results
4. Conclusions
  • 1. Ardeshiry Lajimi A, Hagh MF, Saki N, Mortaz E, Soleimani M, Rahim F. Feasibility of cell therapy in multiple sclerosis: a systematic review of 83 studies. Int J Hematol Oncol Stem Cell Res. 2013; 7(1): 15-33[PubMed]
  • 2. Radaelli M, Merlini A, Greco R, Sangalli F, Comi G, Ciceri F, et al. Autologous bone marrow transplantation for the treatment of multiple sclerosis. Curr Neurol Neurosci Rep. 2014; 14(9): 478[DOI][PubMed]
  • 3. Holloman JP, Ho CC, Hukki A, Huntley JL, Gallicano GI. The development of hematopoietic and mesenchymal stem cell transplantation as an effective treatment for multiple sclerosis. Am J Stem Cells. 2013; 2(2): 95-107[PubMed]
  • 4. Sahraian MA, Bonab MM, Karvigh SA, Yazdanbakhsh S, Nikbin B, Lotfi J. Intrathecal Mesenchymal Stem Cell Therapy in Multiple Sclerosis: A Follow-Up Study for Five Years After Injection. Arch Neurosci. 2014; 1(2): 71-5
  • 5. Thelen JM, Lynch SG, Bruce AS, Hancock LM, Bruce JM. Polypharmacy in multiple sclerosis: relationship with fatigue, perceived cognition, and objective cognitive performance. J Psychosom Res. 2014; 76(5): 400-4[DOI][PubMed]
  • 6. Mohyeddin Bonab M, Mohajeri M, Sahraian MA, Yazdanifar M, Aghsaie A, Farazmand A, et al. Evaluation of cytokines in multiple sclerosis patients treated with mesenchymal stem cells. Arch Med Res. 2013; 44(4): 266-72[DOI][PubMed]
  • 7. Zafranskaya MM, Nizheharodova DB, Yurkevich MY, Lamouskaya NV, Motuzova YM, Bagatka SS, et al. In vitro assessment of mesenchymal stem cells immunosuppressive potential in multiple sclerosis patients. Immunol Lett. 2013; 149(1-2): 9-18[DOI][PubMed]
  • 8. Silani V, Cova L. Stem cell transplantation in multiple sclerosis: safety and ethics. J Neurol Sci. 2008; 265(1-2): 116-21[DOI][PubMed]
  • 9. Broadley SA, Barnett MH, Boggild M, Brew BJ, Butzkueven H, Heard R, et al. Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 1 historical and established therapies. MS Neurology Group of the Australian and New Zealand Association of Neurologists. J Clin Neurosci. 2014; 21(11): 1835-46[DOI][PubMed]
  • 10. Zhao C, Zawadzka M, Roulois AJ, Bruce CC, Franklin RJ. Promoting remyelination in multiple sclerosis by endogenous adult neural stem/precursor cells: defining cellular targets. J Neurol Sci. 2008; 265(1-2): 12-6[DOI][PubMed]
  • 11. Fassas A, Kimiskidis VK. Autologous hemopoietic stem cell transplantation in the treatment of multiple sclerosis: rationale and clinical experience. J Neurol Sci. 2004; 223(1): 53-8[DOI][PubMed]
  • 12. Shevchenko YL, Novik AA, Kuznetsov AN, Afanasiev BV, Lisukov IA, Kozlov VA, et al. High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis. Exp Hematol. 2008; 36(8): 922-8[DOI][PubMed]
  • 13. Keegan BM, Noseworthy JH. Multiple sclerosis. Annu Rev Med. 2002; 53: 285-302[DOI][PubMed]
  • 14. Steinman L. Multiple sclerosis: a two-stage disease. Nat Immunol. 2001; 2(9): 762-4[DOI][PubMed]
  • 15. Chandran S, Compston A. Neural stem cells as a potential source of oligodendrocytes for myelin repair. J Neurol Sci. 2005; 233(1-2): 179-81[DOI][PubMed]
  • 16. Corboy JR, Goodin DS, Frohman EM. Disease-modifying Therapies for Multiple Sclerosis. Curr Treat Options Neurol. 2003; 5(1): 35-54[PubMed]
  • 17. Miller DH, Khan OA, Sheremata WA, Blumhardt LD, Rice GP, Libonati MA, et al. A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2003; 348(1): 15-23[DOI][PubMed]
  • 18. Teixeira MZ. Immunomodulatory drugs (natalizumab), worsening of multiple sclerosis, rebound effect and similitude. Homeopathy. 2013; 102(3): 215-24[DOI][PubMed]
  • 19. Kremenchutzky M, O'Connor P, Hohlfeld R, Zhang-Auberson L, von Rosenstiel P, Meng X, et al. Impact of prior treatment status and reasons for discontinuation on the efficacy and safety of fingolimod: Subgroup analyses of the Fingolimod Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) study. Mult Scler Relat Disord. 2014; 3(3): 341-9[DOI][PubMed]
  • 20. Mancardi G, Saccardi R. Autologous haematopoietic stem-cell transplantation in multiple sclerosis. Lancet Neurol. 2008; 7(7): 626-36[DOI][PubMed]
  • 21. Fernandez O, Oreja-Guevara C, Arroyo R, Izquierdo G, Perez JL, Montalban X. Natalizumab treatment of multiple sclerosis in Spain: results of an extensive observational study. J Neurol. 2012; 259(9): 1814-23[DOI][PubMed]
  • 22. Bar-Or A, Pachner A, Menguy-Vacheron F, Kaplan J, Wiendl H. Teriflunomide and its mechanism of action in multiple sclerosis. Drugs. 2014; 74(6): 659-74[DOI][PubMed]
  • 23. Payne N, Siatskas C, Bernard CC. The promise of stem cell and regenerative therapies for multiple sclerosis. J Autoimmun. 2008; 31(3): 288-94[DOI][PubMed]
  • 24. Spain RI, Cameron MH, Bourdette D. Recent developments in multiple sclerosis therapeutics. BMC Med. 2009; 7: 74[DOI][PubMed]
  • 25. Munzel EJ, Williams A. Promoting remyelination in multiple sclerosis-recent advances. Drugs. 2013; 73(18): 2017-29[DOI][PubMed]
  • 26. Keirstead HS. Stem cells for the treatment of myelin loss. Trends Neurosci. 2005; 28(12): 677-83[DOI][PubMed]
  • 27. Pluchino S, Zanotti L, Brini E, Ferrari S, Martino G. Regeneration and repair in multiple sclerosis: the role of cell transplantation. Neurosci Lett. 2009; 456(3): 101-6[DOI][PubMed]
  • 28. Huang JK, Franklin RJ. Regenerative medicine in multiple sclerosis: identifying pharmacological targets of adult neural stem cell differentiation. Neurochem Int. 2011; 59(3): 329-32[DOI][PubMed]
  • 29. Ben-Hur T. Cell therapy for multiple sclerosis. Neurotherapeutics. 2011; 8(4): 625-42[DOI][PubMed]
  • 30. Riordan NH, Ichim TE, Min WP, Wang H, Solano F, Lara F, et al. Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis. J Transl Med. 2009; 7: 29[DOI][PubMed]
  • 31. Rice CM, Kemp K, Wilkins A, Scolding NJ. Cell therapy for multiple sclerosis: an evolving concept with implications for other neurodegenerative diseases. Lancet. 2013; 382(9899): 1204-13[DOI][PubMed]
  • 32. Lassmann H. Stem cell and progenitor cell transplantation in multiple sclerosis: the discrepancy between neurobiological attraction and clinical feasibility. J Neurol Sci. 2005; 233(1-2): 83-6[DOI][PubMed]
  • 33. Rice C, Halfpenny C, Scolding N. Cell therapy in demyelinating diseases. NeuroRx. 2004; 1(4): 415-23[DOI][PubMed]
  • 34. Pluchino S, Martino G. The therapeutic plasticity of neural stem/precursor cells in multiple sclerosis. J Neurol Sci. 2008; 265(1-2): 105-10[DOI][PubMed]
  • 35. Einstein O, Ben-Hur T. The changing face of neural stem cell therapy in neurologic diseases. Arch Neurol. 2008; 65(4): 452-6[DOI][PubMed]
  • 36. Brundin L, Brismar H, Danilov AI, Olsson T, Johansson CB. Neural stem cells: a potential source for remyelination in neuroinflammatory disease. Brain Pathol. 2003; 13(3): 322-8[PubMed]
  • 37. Nait-Oumesmar B, Picard-Riera N, Kerninon C, Decker L, Seilhean D, Hoglinger GU, et al. Activation of the subventricular zone in multiple sclerosis: evidence for early glial progenitors. Proc Natl Acad Sci U S A. 2007; 104(11): 4694-9[DOI][PubMed]
  • 38. Einstein O, Grigoriadis N, Mizrachi-Kol R, Reinhartz E, Polyzoidou E, Lavon I, et al. Transplanted neural precursor cells reduce brain inflammation to attenuate chronic experimental autoimmune encephalomyelitis. Exp Neurol. 2006; 198(2): 275-84[DOI][PubMed]
  • 39. Ben-Hur T, van Heeswijk RB, Einstein O, Aharonowiz M, Xue R, Frost EE, et al. Serial in vivo MR tracking of magnetically labeled neural spheres transplanted in chronic EAE mice. Magn Reson Med. 2007; 57(1): 164-71[DOI][PubMed]
  • 40. Ben-Hur T, Einstein O, Mizrachi-Kol R, Ben-Menachem O, Reinhartz E, Karussis D, et al. Transplanted multipotential neural precursor cells migrate into the inflamed white matter in response to experimental autoimmune encephalomyelitis. Glia. 2003; 41(1): 73-80[DOI][PubMed]
  • 41. Weiss S, Dunne C, Hewson J, Wohl C, Wheatley M, Peterson AC, et al. Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis. J Neurosci. 1996; 16(23): 7599-609[PubMed]
  • 42. Einstein O, Fainstein N, Vaknin I, Mizrachi-Kol R, Reihartz E, Grigoriadis N, et al. Neural precursors attenuate autoimmune encephalomyelitis by peripheral immunosuppression. Ann Neurol. 2007; 61(3): 209-18[DOI][PubMed]
  • 43. Ben-Hur T. Immunomodulation by neural stem cells. J Neurol Sci. 2008; 265(1-2): 102-4[DOI][PubMed]
  • 44. Pluchino S, Gritti A, Blezer E, Amadio S, Brambilla E, Borsellino G, et al. Human neural stem cells ameliorate autoimmune encephalomyelitis in non-human primates. Ann Neurol. 2009; 66(3): 343-54[DOI][PubMed]
  • 45. Quesenberry PJ, Dooner G, Colvin G, Abedi M. Stem cell biology and the plasticity polemic. Exp Hematol. 2005; 33(4): 389-94[DOI][PubMed]
  • 46. Lindvall O, Kokaia Z. Stem cells for the treatment of neurological disorders. Nature. 2006; 441(7097): 1094-6[DOI][PubMed]
  • 47. Yandava BD, Billinghurst LL, Snyder EY. "Global" cell replacement is feasible via neural stem cell transplantation: evidence from the dysmyelinated shiverer mouse brain. Proc Natl Acad Sci U S A. 1999; 96(12): 7029-34[PubMed]
  • 48. Hammang JP, Archer DR, Duncan ID. Myelination following transplantation of EGF-responsive neural stem cells into a myelin-deficient environment. Exp Neurol. 1997; 147(1): 84-95[DOI][PubMed]
  • 49. Milward EA, Lundberg CG, Ge B, Lipsitz D, Zhao M, Duncan ID. Isolation and transplantation of multipotential populations of epidermal growth factor-responsive, neural progenitor cells from the canine brain. J Neurosci Res. 1997; 50(5): 862-71[PubMed]
  • 50. Kohama I, Lankford KL, Preiningerova J, White FA, Vollmer TL, Kocsis JD. Transplantation of cryopreserved adult human Schwann cells enhances axonal conduction in demyelinated spinal cord. J Neurosci. 2001; 21(3): 944-50[PubMed]
  • 51. Barnett SC, Alexander CL, Iwashita Y, Gilson JM, Crowther J, Clark L, et al. Identification of a human olfactory ensheathing cell that can effect transplant-mediated remyelination of demyelinated CNS axons. Brain. 2000; 123 ( Pt 8): 1581-8[PubMed]
  • 52. Kato T, Honmou O, Uede T, Hashi K, Kocsis JD. Transplantation of human olfactory ensheathing cells elicits remyelination of demyelinated rat spinal cord. Glia. 2000; 30(3): 209-18[PubMed]
  • 53. Imaizumi T, Lankford KL, Burton WV, Fodor WL, Kocsis JD. Xenotransplantation of transgenic pig olfactory ensheathing cells promotes axonal regeneration in rat spinal cord. Nat Biotechnol. 2000; 18(9): 949-53[DOI][PubMed]
  • 54. Pluchino S, Quattrini A, Brambilla E, Gritti A, Salani G, Dina G, et al. Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature. 2003; 422(6933): 688-94[DOI][PubMed]
  • 55. Magalon K, Cantarella C, Monti G, Cayre M, Durbec P. Enriched environment promotes adult neural progenitor cell mobilization in mouse demyelination models. Eur J Neurosci. 2007; 25(3): 761-71[DOI][PubMed]
  • 56. Karussis D, Kassis I, Kurkalli BG, Slavin S. Immunomodulation and neuroprotection with mesenchymal bone marrow stem cells (MSCs): a proposed treatment for multiple sclerosis and other neuroimmunological/neurodegenerative diseases. J Neurol Sci. 2008; 265(1-2): 131-5[DOI][PubMed]
  • 57. Zhang J, Li Y, Chen J, Cui Y, Lu M, Elias SB, et al. Human bone marrow stromal cell treatment improves neurological functional recovery in EAE mice. Exp Neurol. 2005; 195(1): 16-26[DOI][PubMed]
  • 58. Pluchino S, Zanotti L, Brambilla E, Rovere-Querini P, Capobianco A, Alfaro-Cervello C, et al. Immune regulatory neural stem/precursor cells protect from central nervous system autoimmunity by restraining dendritic cell function. PLoS One. 2009; 4(6)[DOI][PubMed]
  • 59. Makar TK, Trisler D, Sura KT, Sultana S, Patel N, Bever CT. Brain derived neurotrophic factor treatment reduces inflammation and apoptosis in experimental allergic encephalomyelitis. J Neurol Sci. 2008; 270(1-2): 70-6[DOI][PubMed]
  • 60. Portmann-Lanz CB, Schoeberlein A, Portmann R, Mohr S, Rollini P, Sager R, et al. Turning placenta into brain: placental mesenchymal stem cells differentiate into neurons and oligodendrocytes. Am J Obstet Gynecol. 2010; 202(3): 2940-29400000000000[DOI][PubMed]
  • 61. Lue J, Lin G, Ning H, Xiong A, Lin CS, Glenn JS. Transdifferentiation of adipose-derived stem cells into hepatocytes: a new approach. Liver Int. 2010; 30(6): 913-22[DOI][PubMed]
  • 62. Zhang Q, Shi S, Liu Y, Uyanne J, Shi Y, Shi S, et al. Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis. J Immunol. 2009; 183(12): 7787-98[DOI][PubMed]
  • 63. Saki N, Abroun S, Farshdousti Hagh M, Asgharei F. Neoplastic bone marrow niche: hematopoietic and mesenchymal stem cells. Cell J. 2011; 13(3): 131-6[PubMed]
  • 64. Jackson WM, Nesti LJ, Tuan RS. Potential therapeutic applications of muscle-derived mesenchymal stem and progenitor cells. Expert Opin Biol Ther. 2010; 10(4): 505-17[DOI][PubMed]
  • 65. Dehghani Fard A, Saki N, Ahmadvand M, Mahmoodinia Maymand M, Mosahebi Mohammadi M, Soleimani M. Mesenchymal Stem Cell; Biology, Application and Its Role in Regenerative Medicine. Sci J Blood Transfus Organ. 2012; 8(4): 306-20
  • 66. Krampera M, Sartoris S, Liotta F, Pasini A, Angeli R, Cosmi L, et al. Immune regulation by mesenchymal stem cells derived from adult spleen and thymus. Stem Cells Dev. 2007; 16(5): 797-810[DOI][PubMed]
  • 67. Reger RL, Tucker AH, Wolfe MR. Differentiation and characterization of human MSCs. Methods Mol Biol. 2008; 449: 93-107[DOI][PubMed]
  • 68. Delorme B, Nivet E, Gaillard J, Haupl T, Ringe J, Deveze A, et al. The human nose harbors a niche of olfactory ectomesenchymal stem cells displaying neurogenic and osteogenic properties. Stem Cells Dev. 2010; 19(6): 853-66[DOI][PubMed]
  • 69. in 't Anker PS, Noort WA, Scherjon SA, Kleijburg-van der Keur C, Kruisselbrink AB, van Bezooijen RL, et al. Mesenchymal stem cells in human second-trimester bone marrow, liver, lung, and spleen exhibit a similar immunophenotype but a heterogeneous multilineage differentiation potential. Haematologica. 2003; 88(8): 845-52[PubMed]
  • 70. Dazzi F, Krampera M. Mesenchymal stem cells and autoimmune diseases. Best Pract Res Clin Haematol. 2011; 24(1): 49-57[DOI][PubMed]
  • 71. Frohman EM, Racke MK, Raine CS. Multiple sclerosis--the plaque and its pathogenesis. N Engl J Med. 2006; 354(9): 942-55[DOI][PubMed]
  • 72. Uccelli A, Laroni A, Freedman MS. Mesenchymal stem cells for the treatment of multiple sclerosis and other neurological diseases. Lancet Neurol. 2011; 10(7): 649-56[DOI][PubMed]
  • 73. Cohen JA. Mesenchymal stem cell transplantation in multiple sclerosis. J Neurol Sci. 2013; 333(1-2): 43-9[DOI][PubMed]
  • 74. Slavin S, Kurkalli BG, Karussis D. The potential use of adult stem cells for the treatment of multiple sclerosis and other neurodegenerative disorders. Clin Neurol Neurosurg. 2008; 110(9): 943-6[DOI][PubMed]
  • 75. Gregory CA, Prockop DJ, Spees JL. Non-hematopoietic bone marrow stem cells: molecular control of expansion and differentiation. Exp Cell Res. 2005; 306(2): 330-5[DOI][PubMed]
  • 76. Harris VK, Yan QJ, Vyshkina T, Sahabi S, Liu X, Sadiq SA. Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis. J Neurol Sci. 2012; 313(1-2): 167-77[DOI][PubMed]
  • 77. Karussis D, Karageorgiou C, Vaknin-Dembinsky A, Gowda-Kurkalli B, Gomori JM, Kassis I, et al. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol. 2010; 67(10): 1187-94[DOI][PubMed]
  • 78. Yamout B, Hourani R, Salti H, Barada W, El-Hajj T, Al-Kutoubi A, et al. Bone marrow mesenchymal stem cell transplantation in patients with multiple sclerosis: a pilot study. J Neuroimmunol. 2010; 227(1-2): 185-9[DOI][PubMed]
  • 79. Zhang YJ, Zhang W, Lin CG, Ding Y, Huang SF, Wu JL, et al. Neurotrophin-3 gene modified mesenchymal stem cells promote remyelination and functional recovery in the demyelinated spinal cord of rats. J Neurol Sci. 2012; 313(1-2): 64-74[DOI][PubMed]
  • 80. Bonab MM, Sahraian MA, Aghsaie A, Karvigh SA, Hosseinian SM, Nikbin B, et al. Autologous mesenchymal stem cell therapy in progressive multiple sclerosis: an open label study. Curr Stem Cell Res Ther. 2012; 7(6): 407-14[PubMed]
  • 81. Rice CM, Mallam EA, Whone AL, Walsh P, Brooks DJ, Kane N, et al. Safety and feasibility of autologous bone marrow cellular therapy in relapsing-progressive multiple sclerosis. Clin Pharmacol Ther. 2010; 87(6): 679-85[DOI][PubMed]
  • 82. Connick P, Kolappan M, Crawley C, Webber DJ, Patani R, Michell AW, et al. Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study. Lancet Neurol. 2012; 11(2): 150-6[DOI][PubMed]
  • 83. Connick P, Kolappan M, Patani R, Scott MA, Crawley C, He XL, et al. The mesenchymal stem cells in multiple sclerosis (MSCIMS) trial protocol and baseline cohort characteristics: an open-label pre-test: post-test study with blinded outcome assessments. Trials. 2011; 12: 62[DOI][PubMed]
  • 84. Harris VK, Faroqui R, Vyshkina T, Sadiq SA. Characterization of autologous mesenchymal stem cell-derived neural progenitors as a feasible source of stem cells for central nervous system applications in multiple sclerosis. Stem Cells Transl Med. 2012; 1(7): 536-47[DOI][PubMed]
  • 85. Odinak MM, Bisaga GN, Novitskiĭ AV, Tyrenko VV, Fominykh MS, Bilibina AA, et al. Transplantation of Mesenchymal Stem Cells in Multiple Sclerosis. Zh Nevrol Psikhiatr Im S S Korsakova. 2010; 111(2 Pt 2): 72-6
  • 86. Mohajeri M, Farazmand A, Mohyeddin Bonab M, Nikbin B, Minagar A. FOXP3 gene expression in multiple sclerosis patients pre- and post mesenchymal stem cell therapy. Iran J Allergy Asthma Immunol. 2011; 10(3): 155-61[PubMed]
  • 87. Darlington PJ, Boivin MN, Renoux C, Francois M, Galipeau J, Freedman MS, et al. Reciprocal Th1 and Th17 regulation by mesenchymal stem cells: Implication for multiple sclerosis. Ann Neurol. 2010; 68(4): 540-5[DOI][PubMed]
  • 88. Liang J, Zhang H, Hua B, Wang H, Wang J, Han Z, et al. Allogeneic mesenchymal stem cells transplantation in treatment of multiple sclerosis. Mult Scler. 2009; 15(5): 644-6[DOI][PubMed]
  • 89. Mohyeddin Bonab M, Yazdanbakhsh S, Lotfi J, Alimoghaddom K, Talebian F, Hooshmand F, et al. Does mesenchymal stem cell therapy help multiple sclerosis patients? Report of a pilot study. Iran J Immunol. 2007; 4(1): 50-7[PubMed]
  • 90. Lublin FD, Bowen JD, Huddlestone J, Kremenchutzky M, Carpenter A, Corboy JR, et al. Human placenta-derived cells (PDA-001) for the treatment of adults with multiple sclerosis: a randomized, placebo-controlled, multiple-dose study. Mult Scler Relat Disord. 2014; 3(6): 696-704[DOI][PubMed]
  • 91. Muraro PA, Robins H, Malhotra S, Howell M, Phippard D, Desmarais C, et al. T cell repertoire following autologous stem cell transplantation for multiple sclerosis. J Clin Invest. 2014; 124(3): 1168-72[DOI][PubMed]
  • 92. Pasquini MC, Griffith LM, Arnold DL, Atkins HL, Bowen JD, Chen JT, et al. Hematopoietic stem cell transplantation for multiple sclerosis: collaboration of the CIBMTR and EBMT to facilitate international clinical studies. Biol Blood Marrow Transplant. 2010; 16(8): 1076-83[DOI][PubMed]
  • 93. Atkins HL, Freedman MS. Hematopoietic stem cell therapy for multiple sclerosis: top 10 lessons learned. Neurotherapeutics. 2013; 10(1): 68-76[DOI][PubMed]
  • 94. Blanco Y, Saiz A, Carreras E, Graus F. Autologous haematopoietic-stem-cell transplantation for multiple sclerosis. Lancet Neurol. 2005; 4(1): 54-63[DOI][PubMed]
  • 95. Burt RK, Loh Y, Cohen B, Stefoski D, Balabanov R, Katsamakis G, et al. Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. Lancet Neurol. 2009; 8(3): 244-53[DOI][PubMed]
  • 96. Tabatabai G, Bahr O, Mohle R, Eyupoglu IY, Boehmler AM, Wischhusen J, et al. Lessons from the bone marrow: how malignant glioma cells attract adult haematopoietic progenitor cells. Brain. 2005; 128: 2200-11[DOI][PubMed]
  • 97. McCormack PL, Scott LJ. Interferon-beta-1b: a review of its use in relapsing-remitting and secondary progressive multiple sclerosis. CNS Drugs. 2004; 18(8): 521-46[PubMed]
  • 98. Fassas A, Anagnostopoulos A, Kazis A, Kapinas K, Sakellari I, Kimiskidis V, 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): 631-8[DOI][PubMed]
  • 99. Burt RK, Traynor AE, Cohen B, Karlin KH, Davis FA, Stefoski D, et al. T cell-depleted autologous hematopoietic stem cell transplantation for multiple sclerosis: report on the first three patients. Bone Marrow Transplant. 1998; 21(6): 537-41[DOI][PubMed]
  • 100. van Bekkum DW. Stem cell transplantation for autoimmune disorders. Preclinical experiments. Best Pract Res Clin Haematol. 2004; 17(2): 201-22[DOI][PubMed]
  • 101. van Gelder M, van Bekkum DW. Treatment of relapsing experimental autoimmune encephalomyelitis in rats with allogeneic bone marrow transplantation from a resistant strain. Bone Marrow Transplant. 1995; 16(3): 343-51[PubMed]
  • 102. 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): 233-41[PubMed]
  • 103. van Gelder M, van Bekkum DW. Effective treatment of relapsing experimental autoimmune encephalomyelitis with pseudoautologous bone marrow transplantation. Bone Marrow Transplant. 1996; 18(6): 1029-34[PubMed]
  • 104. Takahashi K, Prinz M, Stagi M, Chechneva O, Neumann H. TREM2-transduced myeloid precursors mediate nervous tissue debris clearance and facilitate recovery in an animal model of multiple sclerosis. PLoS Med. 2007; 4(4)[DOI][PubMed]
  • 105. Hickey WF, Kimura H. Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science. 1988; 239(4837): 290-2[PubMed]
  • 106. Priller J, Flugel A, Wehner T, Boentert M, Haas CA, Prinz M, et al. Targeting gene-modified hematopoietic cells to the central nervous system: use of green fluorescent protein uncovers microglial engraftment. Nat Med. 2001; 7(12): 1356-61[DOI][PubMed]
  • 107. Simard AR, Rivest S. Bone marrow stem cells have the ability to populate the entire central nervous system into fully differentiated parenchymal microglia. Faseb j. 2004; 18(9): 998-1000[DOI][PubMed]
  • 108. Flugel A, Bradl M, Kreutzberg GW, Graeber MB. Transformation of donor-derived bone marrow precursors into host microglia during autoimmune CNS inflammation and during the retrograde response to axotomy. J Neurosci Res. 2001; 66(1): 74-82[PubMed]
  • 109. Bechmann I, Goldmann J, Kovac AD, Kwidzinski E, Simburger E, Naftolin F, et al. Circulating monocytic cells infiltrate layers of anterograde axonal degeneration where they transform into microglia. Faseb j. 2005; 19(6): 647-9[DOI][PubMed]
  • 110. Voll RE, Herrmann M, Roth EA, Stach C, Kalden JR, Girkontaite I. Immunosuppressive effects of apoptotic cells. Nature. 1997; 390(6658): 350-1[DOI][PubMed]
  • 111. Savill J, Dransfield I, Gregory C, Haslett C. A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol. 2002; 2(12): 965-75[DOI][PubMed]
  • 112. Serhan CN, Savill J. Resolution of inflammation: the beginning programs the end. Nat Immunol. 2005; 6(12): 1191-7[DOI][PubMed]
  • 113. Xu J, Ji BX, Su L, Dong HQ, Sun XJ, Liu CY. Clinical outcomes after autologous haematopoietic stem cell transplantation in patients with progressive multiple sclerosis. Chin Med J (Engl). 2006; 119(22): 1851-5[PubMed]
  • 114. Tyndall A, Matucci-Cerinic M. Haematopoietic stem cell transplantation for the treatment of systemic sclerosis and other autoimmune disorders. Expert Opin Biol Ther. 2003; 3(7): 1041-9[DOI][PubMed]
  • 115. Saiz A, Carreras E, Berenguer J, Yague J, Martinez C, Marin P, et al. MRI and CSF oligoclonal bands after autologous hematopoietic stem cell transplantation in MS. Neurology. 2001; 56(8): 1084-9[PubMed]
  • 116. Fassas A, Passweg JR, Anagnostopoulos A, Kazis A, Kozak T, Havrdova E, et al. Hematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study. J Neurol. 2002; 249(8): 1088-97[DOI][PubMed]
  • 117. Mandalfino P, Rice G, Smith A, Klein JL, Rystedt L, Ebers GC. Bone marrow transplantation in multiple sclerosis. J Neurol. 2000; 247(9): 691-5[PubMed]
  • 118. Lu JQ, Storek J, Metz L, Yong VW, Stevens AM, Nash RA, et al. Continued disease activity in a patient with multiple sclerosis after allogeneic hematopoietic cell transplantation. Arch Neurol. 2009; 66(1): 116-20[DOI][PubMed]
  • 119. Gualandi F, Bruno B, Van Lint MT, Luchetti S, Uccelli A, Capello E, et al. Autologous stem cell transplantation for severe autoimmune diseases: a 10-year experience. Ann N Y Acad Sci. 2007; 1110: 455-64[DOI][PubMed]
  • 120. Brustle O, Jones KN, Learish RD, Karram K, Choudhary K, Wiestler OD, et al. Embryonic stem cell-derived glial precursors: a source of myelinating transplants. Science. 1999; 285(5428): 754-6[PubMed]
  • 121. Liu S, Qu Y, Stewart TJ, Howard MJ, Chakrabortty S, Holekamp TF, et al. Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord transplantation. Proc Natl Acad Sci U S A. 2000; 97(11): 6126-31[PubMed]
  • 122. Billon N, Jolicoeur C, Ying QL, Smith A, Raff M. Normal timing of oligodendrocyte development from genetically engineered, lineage-selectable mouse ES cells. J Cell Sci. 2002; 115: 3657-65[PubMed]
  • 123. Chen L, Coleman R, Leang R, Tran H, Kopf A, Walsh CM, et al. Human neural precursor cells promote neurologic recovery in a viral model of multiple sclerosis. Stem Cell Reports. 2014; 2(6): 825-37[DOI][PubMed]
  • 124. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998; 282(5391): 1145-7[PubMed]
  • 125. Reubinoff BE, Pera MF, Fong CY, Trounson A, Bongso A. Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat Biotechnol. 2000; 18(4): 399-404[DOI][PubMed]
  • 126. Reubinoff BE, Itsykson P, Turetsky T, Pera MF, Reinhartz E, Itzik A, et al. Neural progenitors from human embryonic stem cells. Nat Biotechnol. 2001; 19(12): 1134-40[DOI][PubMed]
  • 127. Zhang SC, Wernig M, Duncan ID, Brustle O, Thomson JA. In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat Biotechnol. 2001; 19(12): 1129-33[DOI][PubMed]
  • 128. Li XJ, Hu BY, Jones SA, Zhang YS, Lavaute T, Du ZW, et al. Directed differentiation of ventral spinal progenitors and motor neurons from human embryonic stem cells by small molecules. Stem Cells. 2008; 26(4): 886-93[DOI][PubMed]
  • 129. Martinat C, Bacci JJ, Leete T, Kim J, Vanti WB, Newman AH, et al. Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype. Proc Natl Acad Sci U S A. 2006; 103(8): 2874-9[DOI][PubMed]
  • 130. Pomp O, Brokhman I, Ben-Dor I, Reubinoff B, Goldstein RS. Generation of peripheral sensory and sympathetic neurons and neural crest cells from human embryonic stem cells. Stem Cells. 2005; 23(7): 923-30[DOI][PubMed]
  • 131. Lee G, Kim H, Elkabetz Y, Al Shamy G, Panagiotakos G, Barberi T, et al. Isolation and directed differentiation of neural crest stem cells derived from human embryonic stem cells. Nat Biotechnol. 2007; 25(12): 1468-75[DOI][PubMed]
  • 132. Izrael M, Zhang P, Kaufman R, Shinder V, Ella R, Amit M, et al. Human oligodendrocytes derived from embryonic stem cells: Effect of noggin on phenotypic differentiation in vitro and on myelination in vivo. Mol Cell Neurosci. 2007; 34(3): 310-23[DOI][PubMed]
  • 133. Hu BY, Du ZW, Li XJ, Ayala M, Zhang SC. Human oligodendrocytes from embryonic stem cells: conserved SHH signaling networks and divergent FGF effects. Development. 2009; 136(9): 1443-52[DOI][PubMed]
  • 134. Fazeli AS, Nasrabadi D, Pouya A, Mirshavaladi S, Sanati MH, Baharvand H, et al. Proteome analysis of post-transplantation recovery mechanisms of an EAE model of multiple sclerosis treated with embryonic stem cell-derived neural precursors. J Proteomics. 2013; 94: 437-50[DOI][PubMed]
  • 135. Nistor GI, Totoiu MO, Haque N, Carpenter MK, Keirstead HS. Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation. Glia. 2005; 49(3): 385-96[DOI][PubMed]
  • 136. Hentze H, Graichen R, Colman A. Cell therapy and the safety of embryonic stem cell-derived grafts. Trends Biotechnol. 2007; 25(1): 24-32[DOI][PubMed]
  • 137. Jackson EL, Garcia-Verdugo JM, Gil-Perotin S, Roy M, Quinones-Hinojosa A, VandenBerg S, et al. PDGFR alpha-positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signaling. Neuron. 2006; 51(2): 187-99[DOI][PubMed]
  • 138. Aharonowiz M, Einstein O, Fainstein N, Lassmann H, Reubinoff B, Ben-Hur T. Neuroprotective effect of transplanted human embryonic stem cell-derived neural precursors in an animal model of multiple sclerosis. PLoS One. 2008; 3(9)[DOI][PubMed]
Creative Commons License Except where otherwise noted, this work is licensed under Creative Commons Attribution Non Commercial 4.0 International License .

Search Relations:



Create Citiation Alert
via Google Reader

Readers' Comments