Journal
NATURE MEDICINE
Volume 22, Issue 5, Pages 479-487Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.4066
Keywords
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Funding
- US Veterans Administration (Gordon Mansfield Spinal Cord Injury Consortium)
- US National Institutes of Health [NS042291, GM008349]
- Craig H. Neilsen Foundation
- Bernard and Anne Spitzer Charitable Trust
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Kobayashi Hospital Furate Research Fund
- Japan Society for the Promotion of Science
- Busta Family fund
- Bleser Family fund
- Grants-in-Aid for Scientific Research [15H05989] Funding Source: KAKEN
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The corticospinal tract (CST) is the most important motor system in humans, yet robust regeneration of this projection after spinal cord injury (SCI) has not been accomplished. In murine models of SCI, we report robust corticospinal axon regeneration, functional synapse formation and improved skilled forelimb function after grafting multipotent neural progenitor cells into sites of SCI. Corticospinal regeneration requires grafts to be driven toward caudalized (spinal cord), rather than rostralized, fates. Fully mature caudalized neural grafts also support corticospinal regeneration. Moreover, corticospinal axons can emerge from neural grafts and regenerate beyond the lesion, a process that is potentially related to the attenuation of the glial scar. Rat corticospinal axons also regenerate into human donor grafts of caudal spinal cord identity. Collectively, these findings indicate that spinal cord 'replacement' with homologous neural stem cells enables robust regeneration of the corticospinal projection within and beyond spinal cord lesion sites, achieving a major unmet goal of SCI research and offering new possibilities for clinical translation.
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