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  4. Glial Cell Line-derived Neurotrophic Factor-overexpressing Human Neural Stem/Progenitor Cells Enhance Therapeutic Efficiency in Rat with Traumatic Spinal Cord Injury

Glial Cell Line-derived Neurotrophic Factor-overexpressing Human Neural Stem/Progenitor Cells Enhance Therapeutic Efficiency in Rat with Traumatic Spinal Cord Injury

Exp Neurobiol, 2019 · DOI: https://doi.org/10.5607/en.2019.28.6.679 · Published: December 1, 2019

Spinal Cord InjuryRegenerative MedicineNeurology

Simple Explanation

Spinal cord injury (SCI) leads to motor, sensory, or autonomic dysfunction and complications. This study explores using human neural stem/progenitor cells (hNSPCs) modified to produce glial cell line-derived neurotrophic factor (GDNF) to improve recovery after SCI in rats. The researchers transplanted GDNF-producing hNSPCs into rats with SCI and found that these cells survived, distributed well, and differentiated into neurons and oligodendrocytes. The treatment reduced lesion size, promoted nerve fiber growth, and improved locomotor recovery. The study suggests that using GDNF-modified hNSPCs could be a more effective cell therapy for SCI. This approach may help protect nerve cells, reduce scar tissue, and improve the ability to move after a spinal cord injury.

Study Duration
9 weeks post-transplantation
Participants
Adult male Sprague Dawley rats (290~310 g)
Evidence Level
Not specified

Key Findings

  • 1
    GDNF-hNSPCs showed robust engraftment, long-term survival, an extensive distribution, and increased differentiation into neurons and oligodendroglial cells compared to controls.
  • 2
    Transplantation of GDNF-hNSPCs significantly reduced lesion volume and glial scar formation, promoted neurite outgrowth, axonal regeneration and myelination, increased Schwann cell migration, and improved locomotor recovery.
  • 3
    Grafted GDNF-hNSPCs substantially reversed the increased expression of voltage-gated sodium channels and neuropeptide Y, and elevated expression of GABA in the injured spinal cord, which are involved in the attenuation of neuropathic pain after SCI.

Research Summary

This study investigates the therapeutic potential of human neural stem/progenitor cells (hNSPCs) transduced with glial cell line-derived neurotrophic factor (GDNF) in a rat model of traumatic spinal cord injury (SCI). The results demonstrate that transplantation of GDNF-hNSPCs leads to robust engraftment, reduced lesion volume and glial scar formation, promoted neurite outgrowth and axonal regeneration, and improved locomotor recovery. The study concludes that GDNF-hNSPCs enhance the therapeutic efficiency of hNSPCs-based cell therapy for SCI, suggesting its potential for clinical translation.

Practical Implications

Enhanced Cell Therapy for SCI

GDNF-modified hNSPCs could be a more effective cell therapy for SCI, potentially improving patient outcomes.

Neuroprotection and Regeneration

The treatment may help protect nerve cells, reduce scar tissue, and improve motor function after spinal cord injury.

Clinical Trial Potential

Findings support the investigation of GDNF-hNSPCs in a clinical trial for SCI.

Study Limitations

  • 1
    Further studies are needed to electrophysiologically confirm the functional neural connections between host and donor-derived neurons.
  • 2
    It is difficult to directly compare the improvements of BBB scores between studies because of differing SCI types, injury levels, and GDNF delivery methods.
  • 3
    Effective GDNF delivery methods to relieve neuropathic pain are still under investigation.

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