Molecular Neurobiology

, Volume 49, Issue 2, pp 625–632 | Cite as

Therapeutic Effect of Transplanted Human Wharton’s Jelly Stem Cell-Derived Oligodendrocyte Progenitor Cells (hWJ-MSC-derived OPCs) in an Animal Model of Multiple Sclerosis

  • Elmira Mikaeili AgahEmail author
  • Kazem Parivar
  • Mohammad Taghi Joghataei


Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS). A potential new therapeutic approach for MS is cell transplantation which may promote remyelination. We transplanted human Wharton’s jelly stem cell-derived oligodendrocyte progenitor cells (hWJ-MSC-derived OPCs) into the brain ventricles of mice induced with experimental autoimmune encephalomyelitis (EAE), the animal model of MS. We studied the effect of the transplanted OPCs on the functional and pathological manifestations of the disease. Transplanted hWJ-MSC-derived OPCs significantly reduced the clinical signs of EAE. Histological examinations showed that remyelination was significantly increased after transplantation. These results suggest that hWJ-MSC-derived OPCs promote the regeneration of myelin sheaths in the brain.


Human Wharton’s jelly mesenchymal stem cell Oligodendrocyte progenitor cells Experimental autoimmune encephalomyelitis 



We thank the Iran National Science Foundation for the financial supports (INSF) and the Cellular & Molecular Research Center of Iran University of Medical Sciences for providing us the facilities.


  1. 1.
    Gironi M, Bergami A, Brambilla E, Ruffini F, Furlan R et al (2000) Immunological markers in multiple sclerosis. Neurol Sci 21(4 Suppl 2):S871–S875PubMedCrossRefGoogle Scholar
  2. 2.
    Hemmer B, Cepok S, Nessler S, Sommer N (2002) Pathogenesis of multiple sclerosis: an update on immunology. Curr Opin Neurol 15:227–231PubMedCrossRefGoogle Scholar
  3. 3.
    Lassmann H (2002) Mechanisms of demyelination and tissue destruction in multiple sclerosis. Clin Neurol Neurosurg 104:168–171PubMedCrossRefGoogle Scholar
  4. 4.
    Franklin RJ (2002) Why does remyelination fail in multiple sclerosis? Nat Rev Neurosci 3:705–714PubMedCrossRefGoogle Scholar
  5. 5.
    Kornek B, Storch MK, Weissert R, Wallstroem E, Stefferl A et al (2000) Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions. Am J Pathol 157:267–276PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S et al (1998) Axonal transection in the lesions of multiple sclerosis. N Engl J Med 338:278–285PubMedCrossRefGoogle Scholar
  7. 7.
    Ferguson B, Matyszak MK, Esiri MM, Perry VH (1997) Axonal damage in acute multiple sclerosis lesions. Brain 120:393–399PubMedCrossRefGoogle Scholar
  8. 8.
    Lovas G, Szilagyi N, Majtenyi K, Palkovits M, Komoly S (2000) Axonal changes in chronic demyelinated cervical spinal cord plaques. Brain 123:308–317PubMedCrossRefGoogle Scholar
  9. 9.
    Pluchino S, Zanotti L, Brini E et al (2009) Regeneration and repair in multiple sclerosis: the role of cell transplantation. Neurosci Lett 456:101–106PubMedCrossRefGoogle Scholar
  10. 10.
    Ho TS, Tsai CY, Tsao N, Chow NH, Lei HY (1997) Infiltrated cells in experimental allergic encephalomyelitis by additional intracerebral injection in myelin-basic-protein-sensitizedB6 mice. J Biomed Sci 4:300–307PubMedCrossRefGoogle Scholar
  11. 11.
    Tsai CY, Chow NH, Ho TS, Lei HY (1997) Intracerebral injection of myelin basic protein (MBP) induces inflammation in brain and causes paraplegia in MBP-sensitized B6 mice. Clin Exp Immunol 109:127–133PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Merodio M, Irache JM, Eclancher F, Mirshahi M, Villarroya H (2000) Distribution of albumin nanoparticles in animals induced with the experimental allergic encephalomyelitis. J Drug Target 8:289–303PubMedCrossRefGoogle Scholar
  13. 13.
    Engelhardt B (2006) Molecular mechanisms involved in T cell migration across the blood–brain barrier. J Neural Transm 113:477–485PubMedCrossRefGoogle Scholar
  14. 14.
    Rakic LM, Zlokovic BV, Segal MB, Lipovac MH, Mitrovic DM et al (1989) Effects of sensory-motor cortical lesions on blood–brain permeability in guinea pigs. Metab Brain Dis 4:9–15PubMedCrossRefGoogle Scholar
  15. 15.
    Kennea NL, Waddington SN, Chan J, O’Donoghue K, Yeung D, Taylor DL et al (2009) Differentiation of human fetal mesenchymal stem cells into cells with an oligodendrocyte phenotype. Cell Cycle 8(7):1069–1079PubMedCrossRefGoogle Scholar
  16. 16.
    Louro J, Pearse D (2008) Stem and progenitor cell therapies: recent progress for spinal cord injury repair. Neurol Res 30(1):5–16PubMedCrossRefGoogle Scholar
  17. 17.
    Ogawa S-I, Tokumoto Y, Miyake J, Nagamune T (2011) Induction of oligodendrocyte differentiation from adult human fibroblast-derived induced pluripotent stem cells. In Vitro Cell Dev Biol Anim 47(7):464–469PubMedCrossRefGoogle Scholar
  18. 18.
    Zhang L, Zhang H-T, Hong S-Q, Ma X, Jiang X-D, Xu R-X (2009) Cografted Wharton’s jelly cells-derived neurospheres and BDNF promote functional recovery after rat spinal cord transection. Neurochem Res 34(11):2030–2039PubMedCrossRefGoogle Scholar
  19. 19.
    Shang A-J, Hong S-Q, Xu Q, Wang H-Y, Yang Y, Wang Z-F et al (2011) NT-3-secreting human umbilical cord mesenchymal stromal cell transplantation for the treatment of acute spinal cord injury in rats. Brain Res 1391:102–113PubMedCrossRefGoogle Scholar
  20. 20.
    Margossian T, Reppel L, Makdissy N, Stoltz J-F, Bensoussan D, Huselstein C (2012) Mesenchymal stem cells derived from Wharton’s jelly: comparative phenotype analysis between tissue and in vitro expansion. Biomed Mater Eng 22(4):243–254PubMedGoogle Scholar
  21. 21.
    Kerschensteiner M, Stadelmann C, Buddeberg BS, Merkler D, Bareyre FM, Anthony DC, Linington C, Bruck W, Schwab ME (2004) Targeting EAE lesions to a predetermined axonal tract system allows for refined behavioral testing in an animal model of multiple sclerosis. Am J Pathol 164:1455–1469PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Meyer R, Weissert R, Diem R, Storch MK, de Graaf KL, Kramer B, Bahr M (2001) Acute neuronal apoptosis in a rat model of multiple sclerosis. J Neurosci 21:6214–6220PubMedGoogle Scholar
  23. 23.
    Stefferl A, Brehm U, Storch M, Lambracht-Washington D, Bourquin C, Wonigeit K, Lassmann H, Linington C (1999) Myelin oligodendrocyte glycoprotein induces experimental autoimmune encephalomyelitis in the “resistant” brown Norway rat: disease susceptibility is determined by MHC and MHC-linked effects on the B cell response. J Immunol 163:40–49PubMedGoogle Scholar
  24. 24.
    Wang S, Guan Q, Diao H, Lian D, Zhong R et al (2007) Prolongation of cardiac allograft survival by inhibition of ERK1/2 signaling in a mouse model. Transplantation 83:323–332PubMedCrossRefGoogle Scholar
  25. 25.
    Keirstead HS, Nistor G, Bernal G, Totoiu M, Cloutier F, Sharp K, Steward O (2005) Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J Neurosci 25:4694–4705PubMedCrossRefGoogle Scholar
  26. 26.
    Copray S, Balasubramaniyan V, Levenga J, de Bruijn J, Liem R, Boddeke E (2006) Olig2 over expression induces the in vitro differentiation of neural stem cells into mature oligodendrocytes. Stem Cells 24:1001–1010PubMedCrossRefGoogle Scholar
  27. 27.
    Kennea NL, Waddington SN, Chan J et al (2009) Differentiation of human fetal mesenchymal stem cells into cells with an oligodendrocyte phenotype. Cell Cycle 8(7):1069–1079PubMedCrossRefGoogle Scholar
  28. 28.
    Kang SK, Shin MJ, Jung JS, Kim YG, Kim CH (2006) Autologous adipose tissue-derived stromal cells for treatment of spinal cord injury. Stem Cells Dev 15:583–594PubMedCrossRefGoogle Scholar
  29. 29.
    Luo YC, Zhang HT, Cheng HY et al (2010) Differentiation of cryopreserved human umbilical cord blood-derived stromal cells into cells with an oligodendrocyte phenotype. In Vitro Cell Dev Biol Anim 46(7):585–589PubMedCrossRefGoogle Scholar
  30. 30.
    Totoiu MO, Nistor GI, Lane TE, Keirstead HS (2004) Remyelination, axonal sparing, and locomotor recovery following transplantation of glial-committed progenitor cells into the MHV model of multiple sclerosis. Exp Neurol 187(2):254–265PubMedCrossRefGoogle Scholar
  31. 31.
    Chen H, Zhang Y, Yang Z, Zhang H (2013) Human umbilical cord Wharton’s jelly-derived oligodendrocyte precursor-like cells for axon and myelin sheath regeneration. Neural Regen Res 8:890–899Google Scholar
  32. 32.
    Zhang H-T, Fan J, Cai Y-Q, Zhao S-J, Xue S, Lin J-H et al (2010) Human Wharton’s jelly cells can be induced to differentiate into growth factor-secreting oligodendrocyte progenitor-like cells. Differentiation 79(1):15–20PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Elmira Mikaeili Agah
    • 1
    Email author
  • Kazem Parivar
    • 1
    • 2
  • Mohammad Taghi Joghataei
    • 3
  1. 1.Department of Biology, Science and Research BranchIslamic Azad UniversityTehranIran
  2. 2.Iran National Science Foundation (INSF)TehranIran
  3. 3.Cellular and Molecular Research CenterIran University of Medical SciencesTehranIran

Personalised recommendations