Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cell Transplants Improve Recovery after Cervical Spinal Cord Injury§

Authors

  • Jason Sharp,

    1. Reeve-Irvine Research Center, Sue and Bill Gross Stem Cell Research Center, Department of Anatomy & Neurobiology, School of Medicine, 2111 Gillespie Neuroscience Research Facility, University of California at Irvine, Irvine, California 92697-4292
    Search for more papers by this author
  • Jennifer Frame,

    1. Reeve-Irvine Research Center, Sue and Bill Gross Stem Cell Research Center, Department of Anatomy & Neurobiology, School of Medicine, 2111 Gillespie Neuroscience Research Facility, University of California at Irvine, Irvine, California 92697-4292
    Search for more papers by this author
  • Monica Siegenthaler,

    1. Reeve-Irvine Research Center, Sue and Bill Gross Stem Cell Research Center, Department of Anatomy & Neurobiology, School of Medicine, 2111 Gillespie Neuroscience Research Facility, University of California at Irvine, Irvine, California 92697-4292
    Search for more papers by this author
  • Gabriel Nistor,

    1. Reeve-Irvine Research Center, Sue and Bill Gross Stem Cell Research Center, Department of Anatomy & Neurobiology, School of Medicine, 2111 Gillespie Neuroscience Research Facility, University of California at Irvine, Irvine, California 92697-4292
    Search for more papers by this author
  • Hans S. Keirstead

    Corresponding author
    1. Reeve-Irvine Research Center, Sue and Bill Gross Stem Cell Research Center, Department of Anatomy & Neurobiology, School of Medicine, 2111 Gillespie Neuroscience Research Facility, University of California at Irvine, Irvine, California 92697-4292
    • Reeve-Irvine Research Center, Sue and Bill Gross Stem Cell Research Center, Department of Anatomy and Neurobiology, 2111 Gillespie Neuroscience Research Facility, College of Medicine, University of California at Irvine, Irvine, CA 92697-4292
    Search for more papers by this author
    • Telephone: (949) 824-6213; Fax: (949) 824-5352


  • Author contributions: J.S.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; J.F.: collection and/or assembly of data, manuscript writing; M.S.: collection and/or assembly of data, data analysis and interpretation, manuscript writing; G.N.: provision of study material or patients, collection and/or assembly of data; H.S.K.: conception and design, financial support, administrative support, data analysis and interpretation, manuscript writing, final approval of manuscript.

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

  • §

    First published online in STEM CELLS EXPRESS October 28, 2009.

Abstract

Evidence that cell transplants can improve recovery outcomes in spinal cord injury (SCI) models substantiates treatment strategies involving cell replacement for humans with SCI. Most pre-clinical studies of cell replacement in SCI examine thoracic injury models. However, as most human injuries occur at the cervical level, it is critical to assess potential treatments in cervical injury models and examine their effectiveness using at-level histological and functional measures. To directly address cervical SCI, we used a C5 midline contusion injury model and assessed the efficacy of a candidate therapeutic for thoracic SCI in this cervical model. The contusion generates reproducible, bilateral movement and histological deficits, although a number of injury parameters such as acute severity of injury, affected gray-to-white matter ratio, extent of endogenous remyelination, and at-level locomotion deficits do not correspond with these parameters in thoracic SCI. On the basis of reported benefits in thoracic SCI, we transplanted human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into this cervical model. hESC-derived OPC transplants attenuated lesion pathogenesis and improved recovery of forelimb function. Histological effects of transplantation included robust white and gray matter sparing at the injury epicenter and, in particular, preservation of motor neurons that correlated with movement recovery. These findings further our understanding of the histopathology and functional outcomes of cervical SCI, define potential therapeutic targets, and support the use of these cells as a treatment for cervical SCI. STEM CELLS 2010;28:152–163

Ancillary