Temporary induction of hypoxic adaptations by preconditioning fails to enhance Schwann cell transplant survival after spinal cord injury

Glia, 2023 · DOI: 10.1002/glia.24302 · Published: March 1, 2023

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates whether preconditioning Schwann cells (SCs) with hypoxia-related treatments before transplantation into a rat model of spinal cord injury (SCI) can improve their survival and promote functional recovery. Hypoxic preconditioning was induced in SCs prior to transplantation by exposure to either low oxygen (1% O2) or pharmacological agents (deferoxamine or adaptaquin). The experiments showed that while preconditioning induced hypoxic adaptations and, in some cases, reduced oxidative stress and enhanced vascularization, it did not improve the survival of transplanted cells or the recovery of sensory or motor function after SCI.

Study Duration

9 Weeks

Participants

276 adult female Fischer 344 rats

Evidence Level

Not specified

Key Findings

1
Hypoxia-related preconditioning, using either low oxygen or pharmacological agents, did not enhance the survival of Schwann cells transplanted into the injured spinal cord.
2
Pharmacological preconditioning attenuated spinal cord oxidative stress and enhanced transplant vascularization.
3
The adaptive changes induced by preconditioning were temporary, lasting less than 24 hours post-transplantation, which may be too short to protect cells during the peak of transplanted cell death.

Research Summary

The study tested whether preconditioning Schwann cells (SCs) to induce hypoxia-related adaptations could improve transplant survival and functional outcomes in a rat model of spinal cord injury (SCI). Preconditioning methods included exposure to low oxygen or pharmacological agents (deferoxamine and adaptaquin), which induced hypoxic adaptations but did not enhance SC survival or functional recovery. The benefits of hypoxia-related adaptations induced by preconditioning for cell transplant therapies are not universal.

Practical Implications

Cell therapy optimization

The study suggests that preconditioning strategies need to be carefully evaluated for specific cell types and injury contexts to ensure they provide the intended benefits.

Oxidative stress management

Although preconditioning did not improve cell survival, the reduction in oxidative stress with certain methods indicates that targeting oxidative stress could be a relevant strategy in SCI therapies.

Timing of interventions

The transient nature of the induced adaptations highlights the importance of considering the timing and duration of preconditioning effects in relation to the mechanisms of cell death after transplantation.

Study Limitations

1
The study was conducted in a rat model, and the results may not directly translate to human SCI.
2
The duration of hypoxic adaptations induced by preconditioning was short-lived, potentially limiting the protective effects.
3
Only Schwann cells were investigated; other cell types may respond differently to hypoxic preconditioning in the context of SCI.

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