ICV-transplanted human glial precursor cells are short-lived yet exert immunomodulatory effects in mice with EAE

Authors

  • Heechul Kim,

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

    1. Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland
    2. Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering,The Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • Naser Muja,

    1. Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland
    2. Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering,The Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • James T. Campanelli,

    1. Q Therapeutics, Inc., 615 Arapeen Dr., Ste. 102, Salt Lake City, Utah
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  • Jeff W.M. Bulte

    Corresponding author
    1. Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland
    2. Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering,The Johns Hopkins University School of Medicine, Baltimore, Maryland
    3. Department of Chemical and Biomolecular Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland
    4. Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland
    • Department of Radiology and Institute for Cell Engineering, The Johns Hopkins University School of Medicine, 217 Traylor Bldg, 720 Rutland Ave, Baltimore, MD 21205-2195, USA
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Abstract

Human glial precursor cells (hGPs) have potential for remyelinating lesions and are an attractive cell source for cell therapy of multiple sclerosis (MS). To investigate whether transplanted hGPs can affect the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, we evaluated the therapeutic effects of transplanted hGPs together with the in vivo fate of these cells using magnetic resonance imaging (MRI) and bioluminescence imaging (BLI). At 14 days post-EAE induction, mice (n = 19) were intracerebroventricularly (ICV) injected with 5 × 105 hGPs that were magnetically labeled with superparamagnetic iron oxide (SPIO) particles as MR contrast agent and transduced with firefly luciferase for BLI of cell survival. Control mice (n = 18) received phosphate buffered saline (PBS) vehicle only. The severity of EAE clinical disability in the hGP-transplanted group was significantly suppressed (P < 0.05) with concomitant inhibition of ConA and MOG-specific T cell proliferation in the spleen. Astrogliosis was reduced and a lower activity of macrophages and/or microglia was observed in the spinal cord (P < 0.05). On MRI, SPIO signal was detected within the lateral ventricle from 1 day post-transplantation and remained there for up to 34 days. BLI indicated that most cells did not survive beyond 5–10 days, consistent with the lack of detectable migration into the brain parenchyma and the histological presence of an abundance of apoptotic cells. Transplanted hGPs could not be detected in the spleen. We conclude that ICV transplantation of short-lived hGPs can have a remote therapeutic effect through immunomodulation from within the ventricle, without cells directly participating in remyelination. © 2012 Wiley Periodicals, Inc.

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