Molecular and cellular changes in the post-traumatic spinal cord remodeling after autoinfusion of a genetically-enriched leucoconcentrate in a mini-pig model

Neural Regeneration Research, 2023 · DOI: 10.4103/1673-5374.360241 · Published: July 1, 2023

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

This study explores a new gene therapy approach for spinal cord injury (SCI) using genetically modified white blood cells (leucoconcentrate) to deliver therapeutic genes directly to the injury site in mini-pigs. The leucoconcentrate was modified to produce vascular endothelial growth factor (VEGF), glial cell line-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM), all known for their regenerative properties. The results showed improved spinal cord tissue preservation, reduced inflammation, and enhanced nerve regeneration in the treated mini-pigs compared to the control group.

Study Duration

60 days

Participants

11 mature mini-pigs

Evidence Level

Not specified

Key Findings

1
Higher sparing of the grey matter and increased survivability of the spinal cord cells (lower number of Caspase-3-positive cells and decreased expression of Hsp27) was observed.
2
Recovery of synaptophysin expression, indicating improved synaptic function, was noted in the treated group.
3
Prevention of astrogliosis (lower area of glial fibrillary acidic protein-positive astrocytes and ionized calcium binding adaptor molecule 1-positive microglial cells) was evident, suggesting reduced glial scar formation.

Research Summary

This study investigates the efficacy of intravenous infusion of an autologous genetically-enriched leucoconcentrate simultaneously producing recombinant VEGF, GDNF, and NCAM on the remodeling of the spinal cord tissue at the site of damage in mini-pigs with moderate SCI. The therapeutic group showed higher sparing of the grey matter, increased survivability of spinal cord cells, recovery of synaptophysin expression, prevention of astrogliosis, and higher growth rates of regenerating axons. The study concludes that intravenous infusion of the autologous genetically-enriched leucoconcentrate has positive effects on post-traumatic remodeling of nervous tissue in the acute phase of SCI, providing a solid platform for new ex vivo gene therapy.

Practical Implications

New Therapeutic Strategy

The autologous genetically-enriched leucoconcentrate approach represents a promising new therapeutic strategy for spinal cord injury.

Clinical Translation

The findings provide a solid foundation for translating regenerative therapies to clinical neurology.

Personalized Medicine

The use of autologous cells offers a personalized and potentially safer approach to gene therapy.

Study Limitations

1
Limited number of animals in the study
2
Beneficial effects should be confirmed on male mini-pigs as well
3
Additional experiments are needed to optimize leukoconcentrate transduction and dosage

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