Schwann cells transduced with a lentiviral vector encoding Fgf-2 promote motor neuron regeneration following sciatic nerve injury
Allodi, Ilary (Universitat Autònoma de Barcelona. Institut de Neurociències)
Mecollari, Vasil (Netherlands Institute for Neurosciences)
González-Pérez, Francisco (Universitat Autònoma de Barcelona. Institut de Neurociències)
Eggers, Ruben (Netherlands Institute for Neurosciences)
Hoyng, Stefan (Netherlands Institute for Neurosciences)
Verhaagen, Joost (Vrije Universiteit Amsterdam)
Navarro, X. (Xavier) (Universitat Autònoma de Barcelona. Institut de Neurociències)
Udina i Bonet, Esther (Universitat Autònoma de Barcelona. Institut de Neurociències)

Fecha:	2014
Resumen:	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.
Ayudas:	European Commission 214003 European Commission 278612 Instituto de Salud Carlos III PI110464
Derechos:	Tots els drets reservats.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió sotmesa a revisió
Materia:	Axonal growth ; Gene therapy ; Muscle reinnervation ; Trophic factor
Publicado en:	GLIA, Vol. 62 (2014) , p. 1736-1746, ISSN 1098-1136

DOI: 10.1002/glia.22712

29 p, 973.7 KB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Neurociències (INc)
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