Cortical AAV-CNTF Gene Therapy Combined with Intraspinal Mesenchymal Precursor Cell Transplantation Promotes Functional and Morphological Outcomes after Spinal Cord Injury in Adult Rats

Neural Plasticity, 2018 · DOI: https://doi.org/10.1155/2018/9828725 · Published: August 6, 2018

Simple Explanation

This study explores a new approach to treating spinal cord injury (SCI) in rats by combining gene therapy and cell transplantation. The gene therapy involves delivering a protein called ciliary neurotrophic factor (CNTF) to nerve cells in the brain that control movement. The cell transplantation involves injecting mesenchymal precursor cells (MPCs) into the injured spinal cord. The aim is to promote the survival and regrowth of damaged nerve fibers after SCI, ultimately leading to improved movement and reduced tissue damage. Some rats received CNTF gene therapy alone, while others received it in combination with either living or non-living MPCs. The results showed that the combined treatment led to better functional outcomes, reduced cyst size and more nerve fiber growth compared to the control group, suggesting potential benefits of this combined approach for SCI treatment.

Study Duration

56 days

Participants

43 adult female Fischer (F344) rats

Evidence Level

Not specified

Key Findings

1
Treatment with AAV-CNTFmCherry, as well as with AAV-CNTFmCherry combined with rMPCs, yielded functional improvements over AAV-GFP alone, as assessed by open-ﬁeld and Ladderwalk analyses.
2
Cyst size was signiﬁcantly reduced in the AAV-CNTFmCherry plus viable rMPC treatment group.
3
Cortical injections of biotinylated dextran amine (BDA) revealed more BDA-stained axons rostral and alongside cysts in the AAV-CNTFmCherry versus AAV-GFP groups.

Research Summary

This study investigated the potential of CNTF gene therapy, delivered via AAV vectors to corticospinal neurons, to promote plasticity and regeneration of axons after spinal cord injury (SCI) in adult rats. The gene therapy was tested alone and in combination with mesenchymal precursor cell (MPC) transplantation into the injury site. The results indicated that AAV-CNTFmCherry treatment, both alone and combined with MPCs, led to functional improvements compared to the AAV-GFP control group. Notably, the combination of AAV-CNTFmCherry with viable rMPCs significantly reduced cyst size at the lesion site. Morphological analysis revealed increased axonal sprouting and regrowth in the AAV-CNTFmCherry groups, with some axons observed extending beyond the injury site. These findings suggest that CNTF gene therapy has the potential to enhance corticospinal repair after SCI.

Practical Implications

Therapeutic Potential

The study suggests that cortical AAV-CNTF gene therapy, particularly when combined with viable rMPC transplantation, holds promise as a therapeutic approach for SCI.

Axonal Regeneration

The findings highlight the potential of CNTF to promote axonal regeneration and plasticity in the corticospinal tract following SCI.

Combined Therapies

The research supports the idea that combining gene therapy with cell transplantation may offer synergistic benefits in SCI treatment.

Study Limitations

1
Considerable interanimal variability
2
Behavioural tests were continued after BDA was injected which could potentially obscure or increase treatment eﬀects due to the injection-associated injury and surgery
3
The use of (freeze-thawed) nonviable cells as appropriate controls for cell transplantation studies in SCI is by no means common

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