The Effects of Controlled Release of Neurotrophin-3 from PCLA Scaffolds on the Survival and Neuronal Differentiation of Transplanted Neural Stem Cells in a Rat Spinal Cord Injury Model

PLoS ONE, 2014 · DOI: 10.1371/journal.pone.0107517 · Published: September 12, 2014

Simple Explanation

Neural stem cells (NSCs) have emerged as a potential source for cell replacement therapy following spinal cord injury (SCI). However, poor survival and low neuronal differentiation remain major obstacles to the use of NSCs. By incorporating NT-3 into a SF coating, we successfully developed NT-3-immobilized scaffolds (membranes and conduits). Sustained release of bioactive NT-3 from the conduits for up to 8 weeks was achieved. These results indicate the feasibility of fabricating NT-3-immobilized scaffolds using the adsorption of NT-3/SF coating method, as well as the potential of these scaffolds to induce SCI repair by promoting survival and neuronal differentiation of transplanted NSCs.

Study Duration

8 weeks

Participants

Adult male rats (220–250 g)

Evidence Level

Not specified

Key Findings

1
NSC neuronal differentiation was 55.264.1% on the NT-3-immobilized membranes, which was significantly higher than that on the NT-3 free membrane.
2
The conduit+NT-3+NSCs group achieved higher NSC survival (75.8615.1%) and neuronal differentiation (21.565.2%) compared with the conduit+NSCs group.
3
The animals that received the conduit+NT-3+ NSCs treatment also showed improved functional outcomes, as well as increased axonal regeneration.

Research Summary

In this study, by incorporating NT-3 into a SF coating, we successfully developed NT-3-immobilized scaffolds (membranes and conduits). Furthermore, 8 weeks after the NSCs were seeded into conduits and implanted in rats with a transected SCI, the conduit+NT-3+NSCs group achieved higher NSC survival (75.8615.1%) and neuronal differentiation (21.565.2%) compared with the conduit+NSCs group. These results suggest that PCLA conduits immobilized with NT-3 have the potential for SCI repair by promoting survival and neuronal differentiation of transplanted NSCs.

Practical Implications

Improved NSC Survival

NT-3-immobilized scaffolds enhance the survival of NSCs, which is crucial for effective cell replacement therapy in SCI.

Enhanced Neuronal Differentiation

The scaffolds promote the differentiation of NSCs into neurons, aiding in the reconstruction of neural networks after SCI.

Functional Recovery and Axonal Regeneration

The treatment leads to improved functional outcomes and increased axonal regeneration, indicating potential for restoring motor function.

Study Limitations

1
Complete spinal cord transection is the most severe injury model.
2
NT-3 has a short half-life and easily diffuses through tissue and cerebrospinal fluid.
3
Gene transduction is limited by various problems, including concerns about the safety and efficiency of gene transfection and the potential adverse effects of exogenous gene expression

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