Improvement of Sciatic Nerve Regeneration Using Laminin-Binding Human NGF-β

Wenjie Sun,Jingyu Wang,Hui Ma,Zhifeng Xiao,Jianwu Dai,Changkai Sun,Qianqian Han,Hui Zhao,Bing Chen,Hang Lin,Xiao-Jiang Li

doi:10.1371/journal.pone.0006180

Abstract

BackgroundSciatic nerve injuries often cause partial or total loss of motor, sensory and autonomic functions due to the axon discontinuity, degeneration, and eventual death which finally result in substantial functional loss and decreased quality of life. Nerve growth factor (NGF) plays a critical role in peripheral nerve regeneration. However, the lack of efficient NGF delivery approach limits its clinical applications. We reported here by fusing with the N-terminal domain of agrin (NtA), NGF-β could target to nerve cells and improve nerve regeneration.MethodsLaminin-binding assay and sustained release assay of NGF-β fused with NtA (LBD-NGF) from laminin in vitro were carried out. The bioactivity of LBD-NGF on laminin in vitro was also measured. Using the rat sciatic nerve crush injury model, the nerve repair and functional restoration by utilizing LBD-NGF were tested.FindingsLBD-NGF could specifically bind to laminin and maintain NGF activity both in vitro and in vivo. In the rat sciatic nerve crush injury model, we found that LBD-NGF could be retained and concentrated at the nerve injury sites to promote nerve repair and enhance functional restoration following nerve damages.ConclusionFused with NtA, NGF-β could bind to laminin specifically. Since laminin is the major component of nerve extracellular matrix, laminin binding NGF could target to nerve cells and improve the repair of peripheral nerve injuries.

Highlights

Sciatic nerve injuries are often caused by injections, gunshot wounds, lacerations, contusions, compressions, and iatrogenic causes [1,2]
Since laminin is the major component of nerve extracellular matrix, laminin binding Nerve growth factor (NGF) could target to nerve cells and improve the repair of peripheral nerve injuries
Injuries to sciatic nerves cause partial or total loss of motor, sensory and autonomic functions due to the axon discontinuity, degeneration, and eventual death which result in substantial functional loss and decreased quality of life [3,4]

Summary

Introduction

Sciatic nerve injuries are often caused by injections, gunshot wounds, lacerations, contusions, compressions, and iatrogenic causes [1,2]. Functional deficits caused by nerve injuries can be compensated by regeneration of peripheral nerves. Mostly pharmacotherapeutic, have been tested to enhance functional recovery after sciatic nerve injuries. The identification of neurotrophic factors offers molecular therapy as a potential approach to enhance nerve regeneration. Nerve growth factor (NGF) plays a critical role. Sciatic nerve injuries often cause partial or total loss of motor, sensory and autonomic functions due to the axon discontinuity, degeneration, and eventual death which result in substantial functional loss and decreased quality of life. Nerve growth factor (NGF) plays a critical role in peripheral nerve regeneration. The lack of efficient NGF delivery approach limits its clinical applications. We reported here by fusing with the N-terminal domain of agrin (NtA), NGF-b could target to nerve cells and improve nerve regeneration

Methods

Results

Conclusion