Immunomodulation by Transplanted Human Embryonic Stem Cell-Derived Oligodendroglial Progenitors in Experimental Autoimmune Encephalomyelitis§

Authors

  • Heechul Kim,

    1. Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Cellular Imaging Section and Vascular Biology Program, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Piotr Walczak,

    1. Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Cellular Imaging Section and Vascular Biology Program, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Candace Kerr,

    1. Stem Cell Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Department of Gynecology and Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Chulani Galpoththawela,

    1. Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Department of Gynecology and Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Assaf A. Gilad,

    1. Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Department of Gynecology and Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Naser Muja,

    1. Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Department of Gynecology and Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Jeff W.M. Bulte

    Corresponding author
    1. Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    3. Department of Gynecology and Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    4. Department of Chemical and Biomolecular Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    5. Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    • Department of Radiology and Institute for Cell Engineering, Johns Hopkins University School of Medicine, 217 Traylor Building, 720 Rutland Avenue, Baltimore, Maryland 21205-2195, USA
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    • Telephone: 443-287-0996; Fax: 443-287-7945


  • Author contributions: H.K. and P.W.: conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; C.K.: provision of study material and collection and/or assembly of data; C.G.: collection and/or assembly of data; A.A.G. and N.M.: collection and/or assembly of data, data analysis and interpretation, and manuscript writing; J.W.M.B.: conception and design, financial support, data analysis and interpretation, manuscript writing, and final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS September 4, 2012.

Abstract

Transplantation of embryonic stem cells and their neural derivatives can lead to amelioration of the disease symptoms of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). Oligodendroglial progenitors (OPs), derived from human embryonic stem cells (hESC, HES-1), were labeled with superparamagnetic iron oxide and transduced with luciferase. At 7 days following induction of EAE in C57/BL6 mice, 1 × 106 cells were transplanted in the ventricles of C57/BL6 mice and noninvasively monitored by magnetic resonance and bioluminescence imaging. Cells were found to remain within the cerebroventricular system and did not survive for more than 10 days. However, EAE mice that received hESC-OPs showed a significant improvement in neurological disability scores (0.9 ± 0.2; n = 12) compared to that of control animals (3.3 ± 0.4; n = 12) at day 15 post-transplantation. Histopathologically, transplanted hESC-OPs generated TREM2-positive CD45 cells, increased TIMP-1 expression, confined inflammatory cells within the subarachnoid space, and gave rise to higher numbers of Foxp3-positive regulatory T cells in the spinal cord and spleen. Our results suggest that transplantation of hESC-OPs can alter the pathogenesis of EAE through immunomodulation, potentially providing new avenues for stem cell-based treatment of MS. STEM CELLS 2012;30:2820–2829

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