Early regenerative effects of NGF-transduced Schwann cells in peripheral nerve repair.
Peripheral nerve injury leads to a rapid and robust increase in the synthesis of neurotrophins which guide and support regenerating axons. To further optimize neurotrophin supply at the earliest stages of regeneration, we over-expressed NGF in Schwann cells (SCs) by transducing these cells with a lentiviral vector encoding NGF (NGF-SCs). Transplantation of NGF-SCs in a rat sciatic nerve transection/repair model led to significant increase of NGF levels 2weeks after injury and correspondingly to substantial improvement in axonal regeneration. Numbers of NF200, ChAT and CGRP-positive axon profiles, as well as the gastrocnemius muscle weights, were significantly higher in the NGF-Schwann cell group compared to the animals that received control SCs transduced with a lentiviral vector encoding GFP (GFP-SCs). Comparison with other models of NGF application signifies the important role of this neurotrophin during the early stages of regeneration, and supports the importance of developing combined gene and cell therapy for peripheral nerve repair.
Department of Clinical Neuroscience, Faculty of Medicine, University of Calgary, Calgary, Canada. shakhbazau@gmail.com
Antos
A
Shakhbazau
Jean
J
Kawasoe
Stefan A
SA
Hoyng
Ranjan
R
Kumar
Jan
J
van Minnen
Joost
J
Verhaagen
Rajiv
R
Midha
D000818:Animals; D002478:Cells, Cultured; D015316:Genetic Therapy; D008297:Male; D020932:Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D059348:Peripheral Nerve Injuries / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D012583:Schwann Cells / Q000378:metabolism / Q000637:transplantation*; D012584:Sciatic Nerve / Q000293:injuries / Q000502:physiology; D014161:Transduction, Genetic
D020932:Nerve Growth Factor