Schwann cells transduced with a lentiviral vector encoding Fgf-2 promote motor neuron regeneration following sciatic nerve injury
Research output: Contribution to journal › Journal article › Research › peer-review
Fibroblast growth factor 2 (FGF-2) is a trophic factor expressed by glial cells and different neuronal populations. Addition of FGF-2 to spinal cord and dorsal root ganglia (DRG) explants demonstrated that FGF-2 specifically increases motor neuron axonal growth. To further explore the potential capability of FGF-2 to promote axon regeneration, we produced a lentiviral vector (LV) to overexpress FGF-2 (LV-FGF2) in the injured rat peripheral nerve. Cultured Schwann cells transduced with FGF-2 and added to collagen matrix embedding spinal cord or DRG explants significantly increased motor but not sensory neurite outgrowth. LV-FGF2 was as effective as direct addition of the trophic factor to promote motor axon growth in vitro. Direct injection of LV-FGF2 into the rat sciatic nerve resulted in increased expression of FGF-2, which was localized in the basal lamina of Schwann cells. To investigate the in vivo effect of FGF-2 overexpression on axonal regeneration after nerve injury, Schwann cells transduced with LV-FGF2 were grafted in a silicone tube used to repair the resected rat sciatic nerve. Electrophysiological tests conducted for up to 2 months after injury revealed accelerated and more marked reinnervation of hindlimb muscles in the animals treated with LV-FGF2, with an increase in the number of motor and sensory neurons that reached the distal tibial nerve at the end of follow-up.
Original language | English |
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Journal | Glia |
Volume | 62 |
Issue number | 10 |
Pages (from-to) | 1736-1746 |
Number of pages | 11 |
ISSN | 0894-1491 |
DOIs | |
Publication status | Published - 2014 |
Externally published | Yes |
Bibliographical note
© 2014 Wiley Periodicals, Inc.
- Animals, Axons/physiology, Cell Proliferation/physiology, Cells, Cultured, Coculture Techniques, Female, Fibroblast Growth Factor 2/genetics, Ganglia, Spinal/physiopathology, Genetic Vectors, HEK293 Cells, Hindlimb/physiopathology, Humans, Lentivirus/genetics, Motor Neurons/physiology, Muscle, Skeletal/physiopathology, Nerve Regeneration, Rats, Inbred F344, Schwann Cells/metabolism, Sciatic Nerve/injuries, Sensory Receptor Cells/physiology, Spinal Cord/physiopathology, Tibial Nerve/physiopathology, Tissue Scaffolds
Research areas
ID: 227433606