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Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration
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Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration
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Journal Article
Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration
2016
Overview
Grafting of caudalized rodent or human neural progenitor cells into sites of spinal cord injury enables true regeneration of damaged corticospinal axons in rodents. Regenerating axons form functional synapses within the graft, can extend beyond the lesion site, and help to support functional motor recovery.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 13/51
/ 14/19
/ 14/28
/ Analysis
/ Animals
/ Cicatrix
/ Electrophysiological Phenomena
/ Female
/ Humans
/ Induced Pluripotent Stem Cells
/ Lesions
/ Male
/ Mice
/ Neural Stem Cells - metabolism
/ Neural Stem Cells - pathology
/ Neural Stem Cells - physiology
/ Neural Stem Cells - transplantation
/ Neuroepithelial Cells - physiology
/ Pyramidal Tracts - metabolism
/ Pyramidal Tracts - pathology
/ Pyramidal Tracts - physiology
/ Rats
