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Local delivery of the Neuregulin1 receptor ecto-domain (ecto-ErbB4) has a positive effect on regenerated nerve fiber maturation

Gene Therapy volume 22, pages 901–907 (2015)Cite this article

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Abstract

The Neuregulin/ErbB system plays an important role in the peripheral nervous system, under both normal and pathological conditions. We previously demonstrated that expression of soluble ecto-ErbB4, the released extracellular fragment of the ErbB4 receptor, stimulated glial cell migration in vitro. In this study we examined the possibility of manipulating this system in vivo in order to improve injured peripheral nerve regeneration. Transected rat median nerves of adult female Wistar rats were repaired with a 10-mm-long graft made by muscle-in-vein combined nerve guide previously transduced with either the adeno-associated viral (AAV) vector AAV2-LacZ or AAV2-ecto-ErbB4. Autologous nerve grafts were used as control. Both stereological and functional analyses were performed to assess nerve regeneration. Data show that delivery of soluble ecto-ErbB4 by gene transfer in the muscle-in-vein combined nerve guide has a positive effect on fiber maturation, suggesting that it could represent a potential tool for improving peripheral nerve regeneration.

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Acknowledgements

This work was supported by grants from the European Community's Seventh Framework Programme (FP7-HEALTH-2011) under grant agreement no. 278612 (BIOHYBRID) and by grants from Compagnia di San Paolo (MOVAG).

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Author notes

  1. G Gambarotta and D Pascal: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical and Biological Sciences, Nerve Regeneration Group, University of Torino, Torino, Italy

    G Gambarotta, D Pascal, G Ronchi, M Morano, I Perroteau, S Geuna & S Raimondo

  2. Interdepartmental Centre of Advanced Studies in Neuroscience, Neuroscience Institute of Torino (NIT), University of Torino, Torino, Italy

    G Gambarotta & I Perroteau

  3. Neuroscience Institute Cavalieri Ottolenghi (NICO), Torino, Italy

    G Ronchi, S Geuna & S Raimondo

  4. The Lundbeck Foundation Research Center MIND and Danish Research Institute of Translational Neuroscience DANDRITE, Aarhus University, Denmark

    S B Jager

  5. Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy

    S Moimas, L Zentilin & M Giacca

  6. Department of Medical Sciences, Faculty of Medicine, University of Trieste, Trieste, Italy

    S Moimas & M Giacca

  7. Orthopedics Department, Reconstructive Microsurgery, Trauma Center Hospital (CTO), University of Torino, Torino, Italy

    P Tos

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Correspondence to G Gambarotta.

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Gambarotta, G., Pascal, D., Ronchi, G. et al. Local delivery of the Neuregulin1 receptor ecto-domain (ecto-ErbB4) has a positive effect on regenerated nerve fiber maturation. Gene Ther 22, 901–907 (2015). https://doi.org/10.1038/gt.2015.46

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