Improvement of sciatic nerve regeneration using laminin-binding human NGF-beta.
BACKGROUND
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 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-beta could target to nerve cells and improve nerve regeneration.


METHODS
Laminin-binding assay and sustained release assay of NGF-beta 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.


RESULTS
LBD-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.


CONCLUSIONS
Fused with NtA, NGF-beta 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.
Sun
Wenjie
W
Key laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Sun
Changkai
C
Zhao
Hui
H
Lin
Hang
H
Han
Qianqian
Q
Wang
Jingyu
J
Ma
Hui
H
Chen
Bing
B
Xiao
Zhifeng
Z
Dai
Jianwu
J
D000818:Animals; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D009416:Nerve Regeneration; D011485:Protein Binding; D051381:Rats; D012584:Sciatic Nerve / Q000502:physiology*
D007797:Laminin; D020932:Nerve Growth Factor