Get access

Intravenous administration of human embryonic stem cell-derived neural precursor cells attenuates cuprizone-induced central nervous system (CNS) demyelination

Authors

  • S. J. Crocker,

    Corresponding author
    1. Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT
    2. Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA
      Stephen J. Crocker, Department of Neuroscience, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USA. Tel: +1 860 679 8750; Fax: +1 860 679 7656; E-mail: crocker@uchc.edu
    Search for more papers by this author
  • R. Bajpai,

    1. Stem Cell and Regenerative Medicine Program, Sanford Burnham Medical Research Institute
    Search for more papers by this author
    • Present addresses: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.

  • C. S. Moore,

    1. Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT
    Search for more papers by this author
  • R. F. Frausto,

    1. Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA
    Search for more papers by this author
    • School of Molecular and Microbial Biosciences, University of Sydney Camperdown, NSW 2006, Australia.

  • G. D. Brown,

    1. Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT
    Search for more papers by this author
  • R. R. Pagarigan,

    1. Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT
    Search for more papers by this author
  • J. L. Whitton,

    1. Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA
    Search for more papers by this author
  • A. V. Terskikh

    1. Stem Cell and Regenerative Medicine Program, Sanford Burnham Medical Research Institute
    Search for more papers by this author

Stephen J. Crocker, Department of Neuroscience, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USA. Tel: +1 860 679 8750; Fax: +1 860 679 7656; E-mail: crocker@uchc.edu

Abstract

S. J. Crocker, R. Bajpai, C. S. Moore, R. F. Frausto, G. D. Brown, R. R. Pagarigan, J. L. Whitton and A. V. Terskikh (2011) Neuropathology and Applied Neurobiology37, 643–653

Intravenous administration of human embryonic stem cell-derived neural precursor cells attenuates cuprizone-induced central nervous system (CNS) demyelination

Aims: Previous studies have demonstrated the therapeutic potential for human embryonic stem cell-derived neural precursor cells (hES-NPCs) in autoimmune and genetic animal models of demyelinating diseases. Herein, we tested whether intravenous (i.v.) administration of hES-NPCs would impact central nervous system (CNS) demyelination in a cuprizone model of demyelination. Methods: C57Bl/6 mice were fed cuprizone (0.2%) for 2 weeks and then separated into two groups that either received an i.v. injection of hES-NPCs or i.v. administration of media without these cells. After an additional 2 weeks of dietary cuprizone treatment, CNS tissues were analysed for detection of transplanted cells and differences in myelination in the region of the corpus callosum (CC). Results: Cuprizone-induced demyelination in the CC was significantly reduced in mice treated with hES-NPCs compared with cuprizone-treated controls that did not receive stem cells. hES-NPCs were identified within the brain tissues of treated mice and revealed migration of transplanted cells into the CNS. A limited number of human cells were found to express the mature oligodendrocyte marker, O1, or the astrocyte marker, glial fibrillary acidic protein. Reduced apoptosis and attenuated microglial and astrocytic responses were also observed in the CC of hES-NPC-treated mice. Conclusions: These findings indicated that systemically administered hES-NPCs migrated from circulation into a demyelinated lesion within the CNS and effectively reduced demyelination. Observed reductions in astrocyte and microglial responses, and the benefit of hES-NPC treatment in this model of myelin injury was not obviously accountable to tissue replacement by exogenously administered cells.

Get access to the full text of this article

Ancillary