Evaluation of the Autologous Genetically Enriched Leucoconcentrate on the Lumbar Spinal Cord Morpho-Functional Recovery in a Mini Pig with Thoracic Spine Contusion Injury

Biomedicines, 2023 · DOI: 10.3390/biomedicines11051331 · Published: April 30, 2023

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

This study investigates how spinal cord injuries (SCI) cause changes not only at the injury site but also in distant areas of the spinal cord, peripheral nerves, and muscles. The researchers aimed to see if a genetically modified leucoconcentrate (GEL), enriched with genes that promote nerve protection, could help restore function in these distant areas after SCI in mini pigs. The GEL was designed to produce three neuroprotective factors: VEGF, GDNF, and NCAM. These factors are known to support nerve cell survival, growth, and communication. The study involved injecting the GEL into mini pigs with thoracic spinal cord injuries and then observing the effects on the lumbar spinal cord, tibial nerve, and hind limb muscles over two months. The results showed that the GEL treatment led to positive changes in the lumbar spinal cord, including remodeling of glial cells and increased expression of proteins important for nerve cell communication. The treatment also helped preserve the structure of the tibial nerve and reduce muscle atrophy in the hind limbs, ultimately improving motor recovery.

Study Duration

2 Months

Participants

11 Female adult miniature Vietnamese pot-bellied pigs

Evidence Level

Not specified

Key Findings

1
The autologous genetically enriched leucoconcentrate promoted positive remodeling of macro- and microglial cells in the lumbar spinal cord of treated mini pigs.
2
The treatment led to increased expression of PSD95 and Chat in the lumbar spinal cord, indicating improved synaptic function.
3
The autologous genetically enriched leucoconcentrate helped preserve the number and morphological characteristics of myelinated fibers in the tibial nerve, which correlated with hind limb motor recovery and reduced soleus muscle atrophy.

Research Summary

This study demonstrates that intravenous infusion of autologous genetically enriched leucoconcentrate can positively impact targets distant from the primary spinal cord injury site in mini pigs. The genetically enriched leucoconcentrate simultaneously producing recombinant VEGF, GDNF, and NCAM, suggesting a multitargeted approach to SCI therapy. These ﬁndings open new perspectives for the therapy of SCI and provide a rationale for further investigation of this approach in larger animal models and eventually in clinical trials.

Practical Implications

Novel Therapeutic Strategy

The use of autologous genetically enriched leucoconcentrate represents a promising new avenue for treating spinal cord injuries by targeting multiple sites of injury and promoting neuroregeneration.

Personalized Medicine Approach

The method of genetically enriched leucoconcentrate preparation from the patient’s peripheral blood offers a personalized approach to gene therapy for SCI.

Multitarget Treatment

The study provides evidence that auto-infusion of genetically enriched leucoconcentrate producing recombinant neurotrophic factors and neuronal cell adhesion molecules is a novel, potentially successful approach for multitarget treatment of SCI.

Study Limitations

1
The study was conducted on a small number of animals.
2
Further research is needed to determine the optimal dose, mode of delivery, and pharmacokinetics of the therapeutic molecules.
3
Further experiments with a higher number and different gender of large animals with anatomical, physiological, and biochemical characteristics close to humans in preclinical investigations are needed.

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