TY - JOUR

T1 - Schwann cells transduced with a lentiviral vector encoding Fgf-2 promote motor neuron regeneration following sciatic nerve injury

AU - Allodi, Ilary

AU - Mecollari, Vasil

AU - González-Pérez, Francisco

AU - Eggers, Ruben

AU - Hoyng, Stefan

AU - Verhaagen, Joost

AU - Navarro, Xavier

AU - Udina, Esther

N1 - © 2014 Wiley Periodicals, Inc.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Animals

KW - Axons/physiology

KW - Cell Proliferation/physiology

KW - Cells, Cultured

KW - Coculture Techniques

KW - Female

KW - Fibroblast Growth Factor 2/genetics

KW - Ganglia, Spinal/physiopathology

KW - Genetic Vectors

KW - HEK293 Cells

KW - Hindlimb/physiopathology

KW - Humans

KW - Lentivirus/genetics

KW - Motor Neurons/physiology

KW - Muscle, Skeletal/physiopathology

KW - Nerve Regeneration

KW - Rats, Inbred F344

KW - Schwann Cells/metabolism

KW - Sciatic Nerve/injuries

KW - Sensory Receptor Cells/physiology

KW - Spinal Cord/physiopathology

KW - Tibial Nerve/physiopathology

KW - Tissue Scaffolds

U2 - 10.1002/glia.22712

DO - 10.1002/glia.22712

M3 - Journal article

C2 - 24989458

VL - 62

SP - 1736

EP - 1746

JO - GLIA

JF - GLIA

SN - 0894-1491

IS - 10

ER -