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The Journal of Neuroscience, March 29, 2006, 26(13):3377-3389; doi:10.1523/JNEUROSCI.4184-05.2006

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Development/Plasticity/Repair
Delayed Transplantation of Adult Neural Precursor Cells Promotes Remyelination and Functional Neurological Recovery after Spinal Cord Injury

Soheila Karimi-Abdolrezaee,¹ Eftekhar Eftekharpour,¹ Jian Wang,¹ Cindi M. Morshead,^2,3 and Michael G. Fehlings^1,2,3,4

¹Division of Cell and Molecular Biology, Toronto Western Research Institute, Krembil Neuroscience Center, Toronto, Ontario, Canada M5T 2S8, and ²Department of Surgery, ³Institute of Medical Sciences, and ⁴Division of Neurosurgery, University of Toronto, Ontario, Canada M5S 1A8

Correspondence should be addressed to Dr. Michael G. Fehlings, Krembil Chair in Neural Repair and Regeneration, Division of Neurosurgery, University of Toronto, Toronto Western Hospital, University Health Network, Room 4W-449, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8. Email: michael.fehlings{at}uhn.on.ca

Spinal cord injury (SCI) results in loss of oligodendrocytes demyelination of surviving axons and severe functional impairment. Spontaneous remyelination is limited. Thus, cell replacement therapy is an attractive approach for myelin repair. In this study, we transplanted adult brain-derived neural precursor cells (NPCs) isolated from yellow fluorescent protein-expressing transgenic mice into the injured spinal cord of adult rats at 2 and 8 weeks after injury, which represents the subacute and chronic phases of SCI. A combination of growth factors, the anti-inflammatory drug minocycline, and cyclosporine A immunosuppression was used to enhance the survival of transplanted adult NPCs. Our results show the presence of a substantial number of surviving NPCs in the injured spinal cord up to 10 weeks after transplantation at the subacute stage of SCI. In contrast, cell survival was poor after transplantation into chronic lesions. After subacute transplantation, grafted cells migrated >5 mm rostrally and caudally. The surviving NPCs integrated principally along white-matter tracts and displayed close contact with the host axons and glial cells. Approximately 50% of grafted cells formed either oligodendroglial precursor cells or mature oligodendrocytes. NPC-derived oligodendrocytes expressed myelin basic protein and ensheathed the axons. We also observed that injured rats receiving NPC transplants had improved functional recovery as assessed by the Basso, Beattie, and Bresnahan Locomotor Rating Scale and grid-walk and footprint analyses. Our data provide strong evidence in support of the feasibility of adult NPCs for cell-based remyelination after SCI.

Key words: adult neural precursor cells; spinal cord injury; oligodendrocytes; remyelination; neurological recovery; rat

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Received Oct. 1, 2005; revised Jan. 3, 2006; accepted Feb. 15, 2006.

Correspondence should be addressed to Dr. Michael G. Fehlings, Krembil Chair in Neural Repair and Regeneration, Division of Neurosurgery, University of Toronto, Toronto Western Hospital, University Health Network, Room 4W-449, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8. Email: michael.fehlings{at}uhn.on.ca

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