title: Schwann cells transduced with a lentiviral vector encoding Fgf-2 promote motor neuron regeneration following sciatic nerve injury.
abstract: 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.
authors.affiliation: Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain.
authors.forename: Ilary
authors.initials: I
authors.lastname: Allodi
authors.forename: Vasil
authors.initials: V
authors.lastname: Mecollari
authors.forename: Francisco
authors.initials: F
authors.lastname: González-Pérez
authors.forename: Ruben
authors.initials: R
authors.lastname: Eggers
authors.forename: Stefan
authors.initials: S
authors.lastname: Hoyng
authors.forename: Joost
authors.initials: J
authors.lastname: Verhaagen
authors.forename: Xavier
authors.initials: X
authors.lastname: Navarro
authors.forename: Esther
authors.initials: E
authors.lastname: Udina
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000503:physiopathology; D005822:Genetic Vectors; D057809:HEK293 Cells; D006614:Hindlimb / Q000503:physiopathology; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D009046:Motor Neurons / Q000502:physiology*; D018482:Muscle, Skeletal / Q000503:physiopathology; D009416:Nerve Regeneration; D011916:Rats, Inbred F344; D012583:Schwann Cells / Q000378:metabolism* / Q000637:transplantation*; D012584:Sciatic Nerve / Q000293:injuries* / Q000503:physiopathology; D011984:Sensory Receptor Cells / Q000502:physiology; D013116:Spinal Cord / Q000503:physiopathology; D013979:Tibial Nerve / Q000503:physiopathology; D054457:Tissue Scaffolds
chemical_list: D016222:Fibroblast Growth Factor 2
keywords: axonal growth; gene therapy; muscle reinnervation; trophic factor