Reducing host aldose reductase activity promotes neuronal differentiation of transplanted neural stem cells at spinal cord injury sites and facilitates locomotion recovery

Neural Regeneration Research, 2022 · DOI: https://doi.org/10.4103/1673-5374.330624 · Published: January 7, 2022

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Neural stem cell (NSC) transplantation holds promise for replacing lost neurons after spinal cord injury. The inflammatory environment after injury limits the survival and differentiation of the transplanted cells. This study explores how to modify the inflammatory environment to improve the outcome of NSC transplantation. The researchers focused on aldose reductase (AR), an enzyme involved in glucose metabolism. By inhibiting AR, they aimed to shift the polarization of microglia/macrophages towards an M2 phenotype, which is associated with tissue repair and regeneration. The study found that inhibiting AR promoted M2 polarization, enhanced neuronal differentiation of transplanted NSCs, and improved locomotor functional recovery in mice with spinal cord injuries. These findings suggest that AR inhibition could be a useful strategy for enhancing NSC transplantation outcomes.

Study Duration

5 weeks

Participants

288 mice

Evidence Level

Not specified

Key Findings

1
Inhibition of host aldose reductase (AR) promoted the polarization of microglia/macrophages toward the M2 phenotype in lesioned spinal cord injuries.
2
M2 macrophages promoted the differentiation of NSCs into neurons in vitro.
3
Transplantation of NSCs into injured spinal cords either deficient in AR or treated with the AR inhibitor sorbinil promoted the survival and neuronal differentiation of NSCs and contributed to locomotor functional recovery.

Research Summary

The study investigates the effect of reducing host aldose reductase (AR) activity on neuronal differentiation of transplanted neural stem cells (NSCs) at spinal cord injury (SCI) sites and its impact on locomotion recovery. The key finding is that inhibiting AR activity promotes the polarization of microglia/macrophages toward the M2 phenotype, which in turn enhances the survival and neuronal differentiation of transplanted NSCs. The study concludes that inhibiting host AR activity is beneficial for enhancing the survival and neuronal differentiation of transplanted NSCs, suggesting its potential as a treatment for spinal cord injury.

Practical Implications

Therapeutic Target

Aldose reductase (AR) can be a therapeutic target to modulate the microenvironment of the injured spinal cord, making it more conducive to neural stem cell (NSC) transplantation.

M2 Polarization Strategy

Promoting M2 polarization of microglia/macrophages can enhance neuronal differentiation of transplanted NSCs and improve functional recovery after spinal cord injury.

Clinical Translation

Combining AR inhibitors with NSC transplantation may improve outcomes for patients with spinal cord injuries. Further research is needed to determine the optimal AR inhibitors and NSC delivery methods for clinical application.

Study Limitations

1
The use of mice with global AR deficiency does not exclude the roles of AR in other cell types.
2
Whether these neurons bear the properties of spinal motor neurons or integrate into the spinal circuit remains to be investigated.
3
The study did not exclude the effects of the change of bone morphogenetic protein/Notch signaling in AR-deficient mice.

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