TRANSDUCED SCHWANN CELLS PROMOTE AXON GROWTH AND MYELINATION AFTER SPINAL CORD INJURY

Exp Neurol, 2007 · DOI: 10.1016/j.expneurol.2007.06.023 · Published: October 1, 2007

Simple Explanation

Following a spinal cord injury, the regeneration of axons in the central nervous system is limited, which restricts the restoration of communication between the brain and the body. This can lead to permanent motor and sensory dysfunction. This study explores the use of Schwann cells (SCs), which can be grafted into the injured spinal cord to provide structural support for axonal growth and generate neurotrophic factors. These factors are known to promote axonal growth. The research focuses on using Schwann cells transduced with a bifunctional neurotrophin molecule (D15A) to promote axon growth and myelination after spinal cord injury in rats. D15A mimics the actions of neurotrophin-3 and brain-derived neurotrophic factor.

Study Duration

6 weeks post-implantation

Participants

219 adult female Fischer rats

Evidence Level

Not specified

Key Findings

1
D15A-secreting SC grafts exhibited 5-fold increases in graft volume, SC number and myelinated axon counts and a 3-fold increase in myelinated to unmyelinated (ensheathed) axon ratios.
2
The total number of axons within grafts of LV/GFP/D15A SCs was estimated to be over 70,000.
3
5-HT, DβH, and CGRP axon length was increased up to 5-fold within D15A grafts.

Research Summary

This study investigates the therapeutic potential of utilizing neurotrophin-transduced Schwann cells (SCs) to repair the injured spinal cord in a rat model of contusion. Schwann cells were transduced with adenoviral (AdV) or lentiviral (LV) vectors encoding a bifunctional neurotrophin molecule (D15A) and implanted into the injury center one week after a moderate thoracic (T8) adult rat spinal cord contusion. The results demonstrate that increased neurotrophin secretion by the implanted D15A SCs led to a significantly increased number of axons in the contusion site.

Practical Implications

Therapeutic Potential

Neurotrophin-transduced SCs show promise for repairing injured spinal cords.

Axon Growth

Increased neurotrophin secretion promotes axon growth at the contusion site.

Myelination Enhancement

D15A-secreting SCs increase graft volume and myelinated axon counts.

Study Limitations

1
Qualitative differences were observed between AdV and LV vectors.
2
Neurotrophin levels decreased over time in both LV vector- and AdV vector-transduced SC implants.
3
Behavioral recovery was not improved.

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