Sustained delivery of neurotrophic factors to treat spinal cord injury

Translational Neuroscience, 2021 · DOI: https://doi.org/10.1515/tnsci-2020-0200 · Published: January 1, 2021

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Acute spinal cord injury (SCI) is a severe condition leading to physical and psychological trauma and socioeconomic challenges. Neurons in the spinal cord require neurotrophic factors for survival and reconnection, but these factors are limited endogenously, making sustained delivery challenging. Researchers have explored cellular, viral, and tissue engineering approaches to deliver these factors effectively. Commonly studied neurotrophic factors like BDNF, NT-3, NGF, CNTF, bFGF, and GDNF have short cycles, insufficient for significant neural regeneration after SCI. Various vehicles, including cellular and viral, as well as tissue engineering scaffolds have been tested to deliver neurotrophic factors to the injury site safely and sustainably. This review explores the neurotrophic factors used in SCI treatment trials and the vehicles commonly employed for their sustained delivery. It highlights various methods used to provide continuous neurotrophic support at the SCI site, accelerating neural regeneration and promoting functional recovery.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
Sustained delivery of exogenous neurotrophic factors is necessary to promote neural repair and functional recovery after SCI. The most commonly used exogenous neurotrophic factors include BDNF, neurotrophin-3 (NT-3), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), basic ﬁbroblast growth factor (bFGF), insulin-like growth factor (IGF), and glial cell-derived neurotrophic factor (GDNF).
2
Stem cells, especially MSCs and NSCs, are used to secrete desirable proteins and neurotrophic factors after genetic manipulation, promoting neural and vascular regeneration. A variety of cells, including MSCs, neural stem cells (NSCs), embryonic stem cells (ESCs), olfactory ensheathing cells (OECs) as well as OLs have been used to repair SCI
3
Tissue engineering scaffolds and biomaterials can provide support and guidance for nerve regeneration, acting as carriers for neurotrophic factors and stem cells, forming functional biomaterials to treat SCI. Nerve scaﬀold mate- rials combined with neurotrophic factors and stem cells form functional biomaterials that can be used to treat the SCI

Research Summary

This review discusses the importance of neurotrophic factors in treating spinal cord injuries (SCI) and the challenges associated with their delivery. It emphasizes that neurons need these factors to re-establish connections after injury, but endogenous production is insufficient. The review highlights the use of stem cells and tissue engineering scaffolds as vehicles for the sustained delivery of neurotrophic factors. It also discusses different types of neurotrophic factors, such as BDNF, NT-3, and GDNF, and their respective roles in promoting nerve cell survival, axonal growth, and functional recovery. The study concludes that a combination of neurotrophic factors, cellular and viral vehicles, and tissue engineering materials is necessary to achieve satisfactory functional recovery after acute SCI, given the complex biomechanical changes involved.

Practical Implications

Therapeutic Strategies

Combination therapies involving neurotrophic factors, stem cells, and tissue engineering scaffolds can enhance neural regeneration and functional recovery after SCI.

Drug Delivery Systems

The development of sustained delivery systems, such as mini-osmotic pumps, nanoparticles, and viral vectors, is crucial for maintaining effective concentrations of neurotrophic factors at the injury site.

Clinical Trials

Further human trials are warranted to evaluate the efficacy of combined approaches in treating SCI, considering the complex biomechanical changes post-injury.

Study Limitations

1
Lack of systematic studies comparing optimal timing and duration of neurotrophic factor delivery
2
Potential for long-term vector-mediated expression of growth factors to entrap axons and alter dendritic architecture
3
Absence of reported recovery after total SCI with any single approach

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