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Translational and Clinical Research
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Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cell Transplants Improve Recovery after Cervical Spinal Cord Injury†‡§
Article first published online: 28 OCT 2009
DOI: 10.1002/stem.245
Copyright © 2009 AlphaMed Press
Additional Information
How to Cite
Sharp, J., Frame, J., Siegenthaler, M., Nistor, G. and Keirstead, H. S. (2010), Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cell Transplants Improve Recovery after Cervical Spinal Cord Injury. STEM CELLS, 28: 152–163. doi: 10.1002/stem.245
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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.
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Disclosure of potential conflicts of interest is found at the end of this article.
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First published online in STEM CELLS EXPRESS October 28, 2009.
Publication History
- Issue published online: 12 JAN 2010
- Article first published online: 28 OCT 2009
- Accepted manuscript online: 28 OCT 2009 12:00AM EST
- Manuscript Accepted: 16 OCT 2009
- Manuscript Received: 8 MAY 2009
Funded by
- Geron Corporation
- University of California Discovery Grant
- Roman Reed Spinal Cord Injury Research Fund of California
- Research for Cure, and individual donations to the Reeve-Irvine Research Center
- Bill and Joan Jackson Scholarship
Keywords:
- Spinal cord injury;
- Human embryonic stem cells;
- Forelimb;
- Pathogenesis;
- Neuroprotection
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