期刊
MOLECULAR AND CELLULAR NEUROSCIENCE
卷 50, 期 1, 页码 103-112出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2012.04.004
关键词
NGF; Schwann cells; Lentiviral vector; Peripheral nerve; Regeneration; Gene therapy
资金
- Canadian Institute for Health Research (Regenerative medicine and nanomedicine team grant) [163322]
- Center for excellence in nerve regeneration (partnership between the Hotchkiss Brain Institute, University of Calgary and Integra Life Sciences)
- Alberta Innovates-Health Solutions (AI-HS)
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 2 weeks 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. (c) 2012 Elsevier Inc. All rights reserved.
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