Journal
GLIA
Volume 71, Issue 3, Pages 648-666Publisher
WILEY
DOI: 10.1002/glia.24302
Keywords
adaptaquin; cell survival; deferoxamine; hypoxia adaptations; hypoxia inducible factor; preconditioning; prolyl hydroxylase inhibition; spinal cord injury; transplant
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In this study, the researchers explored whether hypoxia-related preconditioning could protect transplanted Schwann cells into the injured spinal cord. The results showed that hypoxia-related preconditioning did not enhance cell survival or the recovery of sensory and motor function.
Hypoxic preconditioning is protective in multiple models of injury and disease, but whether it is beneficial for cells transplanted into sites of spinal cord injury (SCI) is largely unexplored. In this study, we analyzed whether hypoxia-related preconditioning protected Schwann cells (SCs) transplanted into the contused thoracic rat spinal cord. Hypoxic preconditioning was induced in SCs prior to transplantation by exposure to either low oxygen (1% O-2) or pharmacological agents (deferoxamine or adaptaquin). All preconditioning approaches induced hypoxic adaptations, including increased expression of HIF-1 alpha and its target genes. These adaptations, however, were transient and resolved within 24 h of transplantation. Pharmacological preconditioning attenuated spinal cord oxidative stress and enhanced transplant vascularization, but it did not improve either transplanted cell survival or recovery of sensory or motor function. Together, these experiments show that hypoxia-related preconditioning is ineffective at augmenting either cell survival or the functional outcomes of SC-SCI transplants. They also reveal that the benefits of hypoxia-related adaptations induced by preconditioning for cell transplant therapies are not universal.
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