Glial-Derived Growth Factor and Pleiotrophin Synergistically Promote Axonal Regeneration in Critical Nerve Injuries

Acta Biomater, 2018 · DOI: 10.1016/j.actbio.2018.07.048 · Published: September 15, 2018

Regenerative Medicine Neurology Biomedical

Simple Explanation

This research explores methods for repairing large nerve gaps, which are difficult to heal and often require tissue grafts that cause other complications. The study investigates whether certain growth factors can help nerves regenerate across these gaps using special scaffolds. The scientists found that a combination of two growth factors, GDNF and pleiotrophin (PTN), worked better together than alone. This combination helped nerve fibers grow across a 4 cm gap in rabbits, leading to some recovery of muscle function. However, the regenerated nerves didn't fully recover, showing delays in forming myelin, which is essential for proper nerve function. This suggests that while the growth factors help nerve fibers grow, additional treatments might be needed to improve the quality and speed of nerve recovery.

Study Duration

5 Months

Participants

49 adult female New Zealand White rabbits

Evidence Level

Not specified

Key Findings

1
Pleiotrophin (PTN) and glial-derived neurotrophic factor (GDNF) have a synergistic effect on axonal regeneration in vitro, promoting both sensory and motor neuron growth.
2
In vivo, a combination of PTN-GDNF in multiluminal biosynthetic nerve implants (BNIs) led to improved nerve regeneration across a 4 cm critical gap in rabbits, compared to PTN or GDNF alone.
3
Despite improved axonal regeneration with PTN-GDNF, the regenerated axons showed delayed remyelination and were often found in Remak bundles, suggesting a need for additional strategies to promote proper nerve maturation.

Research Summary

The study addresses the challenge of repairing critical nerve injuries with long gaps, where traditional methods like autografts have limitations. It explores the potential of growth factors, specifically pleiotrophin (PTN) and glial-derived neurotrophic factor (GDNF), to enhance nerve regeneration in these challenging scenarios. In vitro experiments revealed a synergistic effect of PTN and GDNF on both sensory and motor neuron growth. This led to in vivo testing using biosynthetic nerve implants (BNIs) releasing PTN, GDNF, or a combination of both to bridge a 4 cm nerve gap in rabbits. The combination of PTN-GDNF demonstrated improved axonal regeneration across the nerve gap, leading to partial functional recovery in the animals. However, the regenerated nerves exhibited delayed remyelination, indicating the need for further optimization of the regenerative strategy.

Practical Implications

Optimized Growth Factor Delivery

The synergistic effect of PTN-GDNF suggests that combining neurotrophic and pleiotrophic factors is a promising strategy. Future designs should focus on improved growth factor release and gradients.

Targeted Remyelination Strategies

The observed delay in remyelination highlights the importance of incorporating strategies to promote Schwann cell function and myelination in nerve regeneration therapies.

Clinical Translation Potential

The use of biosynthetic nerve implants supplemented with growth factors has the potential to provide an alternative to autografts for treating long nerve gap injuries, offering a less invasive and potentially more effective solution.

Study Limitations

1
The study was performed on rabbits, and results may not directly translate to humans.
2
The functional recovery achieved with PTN-GDNF was only partial, indicating the need for further improvements.
3
The mechanisms underlying the synergistic effect of PTN and GDNF were not fully elucidated.

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