Sponge-mediated Lentivirus Delivery to Acute and Chronic Spinal Cord Injuries

J Control Release, 2015 · DOI: 10.1016/j.jconrel.2015.02.032 · Published: April 28, 2015

Simple Explanation

The study explores a new method for delivering gene therapy to the injured spinal cord using sponges filled with lentiviruses. These sponges are placed in the space around the spinal cord to release regenerative factors over a long period. The researchers tested this method on mice with both acute and chronic spinal cord injuries. They used lentiviruses to deliver a gene called Sonic hedgehog (Shh), which is known to help with spinal cord regeneration. The results showed that the sponge delivery system could successfully introduce genes into the spinal cord, leading to increased regeneration and changes in the types of cells present at the injury site.

Study Duration

12 weeks

Participants

Female mice (C57Bl6, 20g, Charles River), n = 4–5 per condition

Evidence Level

Not specified

Key Findings

1
Lentivirus-filled sponges inserted into the intrathecal space resulted in transgene expression within multiple cell types for 12 weeks in both intact and injured spinal cords.
2
In an acute injury model, sponges placed directly above the injury increased oligodendrocyte presence and decreased astrocyte presence, while sponges placed caudal to the injury had a reduced impact.
3
In a chronic injury model, the lentivirus-filled sponges increased oligodendrocyte presence and decreased astrocyte presence, and the effect of Shh was mediated in part by a reduction of Bmp signaling.

Research Summary

This study introduces a novel method of delivering lentiviruses to the spinal cord using macro-porous sponges inserted into the intrathecal space. This method allows for long-term, localized expression of therapeutic genes without directly injecting into the spinal cord tissue. The researchers found that this sponge-mediated delivery system effectively transduced multiple cell types in both intact and injured spinal cords, and the expression persisted for up to 12 weeks. Delivery of Sonic hedgehog (Shh) via lentivirus-loaded sponges altered the cellular environment of the injured spinal cord, promoting oligodendrocyte presence and decreasing astrocyte presence, which suggests a potential therapeutic benefit for spinal cord regeneration.

Practical Implications

Therapeutic Delivery

The sponge-mediated lentivirus delivery platform offers a less invasive method for delivering gene therapies to the spinal cord, potentially reducing the risk of further injury.

Regenerative Potential

The study demonstrates the potential of Sonic hedgehog (Shh) to modulate the cellular environment in the injured spinal cord, promoting oligodendrocyte presence and decreasing astrocyte presence, which are key factors in spinal cord regeneration.

Timing Considerations

The findings suggest that the timing of therapeutic intervention (acute vs. chronic) and the location of delivery (above vs. caudal to the injury) can influence the outcome of gene therapy for spinal cord injury.

Study Limitations

1
Transgene expression decreased by 12 weeks, potentially due to immune-mediated gene silencing.
2
Lentivirus transport through the spinal cord tissue may be a limiting factor for this delivery method.
3
The study focused on a specific injury model (lateral hemisection) and a single therapeutic gene (Sonic hedgehog), which may limit the generalizability of the findings.

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