Abstract
Restoring function to the injured spinal cord represents one of the most formidable challenges in regenerative medicine. Glial cell transplantation is widely considered to be one of the most promising therapeutic strategies, and several differentiated glial cell types—in particular, Schwann cells and olfactory ensheathing cells (OECs)—have been proposed as transplant candidates. In this Review, we analyze evidence from animal studies for improved functional recovery following transplantation of OECs into spinal cord injuries, and examine the mechanisms by which repair might be achieved. Data obtained using various injury models support the view that OEC transplants can promote functional recovery, but accumulating anatomical evidence indicates that although axons regenerate within a transplant, they do not cross the lesion or reconnect with neurons on the opposite side to any significant extent. Consequently, it is possible that neuroprotection and promotion of sprouting from intact fibers are the main mechanisms that contribute to functional recovery. We conclude that for the foreseeable future the clinical benefits of OEC transplants alone are likely to be modest. The future potential of cell transplantation strategies will probably depend on the success with which the transplants can be combined with other, synergistic, therapies to achieve significant regeneration of axons and re-establish functionally useful connections across a spinal cord injury.
Key Points
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Olfactory ensheathing cells (OECs) are potential candidates for cell transplantation in CNS repair
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In some circumstances, OECs appear to promote functional recovery that is detectable using behavioral tests
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Anatomical evidence suggests that axons can regenerate within a transplant but do not cross a lesion or reconnect with neurons on the opposite side of the lesion
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The main mechanisms that contribute to functional recovery might be neuroprotection and promotion of sprouting from intact fibers
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The clinical benefits of OEC transplantation in patients with spinal cord injuries are likely to be modest
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Acknowledgements
Work in the authors' laboratories is funded by the Multiple Sclerosis Society of Great Britain and Northern Ireland, the Wellcome Trust, the Medical Research Council and the International Spinal Research Trust. SC Barnett is a Multiple Sclerosis Society Senior Research Fellow.
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Barnett, S., Riddell, J. Olfactory ensheathing cell transplantation as a strategy for spinal cord repair—what can it achieve?. Nat Rev Neurol 3, 152–161 (2007). https://doi.org/10.1038/ncpneuro0447
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DOI: https://doi.org/10.1038/ncpneuro0447
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