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Article

Fibroblasts Colonizing Nerve Conduits Express High Levels of Soluble Neuregulin1, a Factor Promoting Schwann Cell Dedifferentiation

by
Benedetta E. Fornasari
1,2,
Marwa El Soury
1,2,
Giulia Nato
2,3,
Alessia Fucini
1,
Giacomo Carta
1,2,
Giulia Ronchi
1,2,
Alessandro Crosio
1,2,4,
Isabelle Perroteau
1,
Stefano Geuna
1,2,
Stefania Raimondo
1,2 and
Giovanna Gambarotta
1,2,*
1
Department of Clinical and Biological Sciences (DSCB), University of Torino, 10043 Orbassano (Torino), Italy
2
Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Torino, 10043 Orbassano (Torino), Italy
3
Department of Life Sciences and Systems Biology (DBIOS), University of Torino, 10123 Torino, Italy
4
Hand Surgery and Reconstructive Microsurgery, Gaetano Pini—CTO Hospital, 20122 Milano, Italy
*
Author to whom correspondence should be addressed.
Cells 2020, 9(6), 1366; https://doi.org/10.3390/cells9061366
Submission received: 25 April 2020 / Revised: 26 May 2020 / Accepted: 30 May 2020 / Published: 1 June 2020
(This article belongs to the Special Issue Schwann Cells: From Formation to Clinical Significance)
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Abstract

Conduits for the repair of peripheral nerve gaps are a good alternative to autografts as they provide a protected environment and a physical guide for axonal re-growth. Conduits require colonization by cells involved in nerve regeneration (Schwann cells, fibroblasts, endothelial cells, macrophages) while in the autograft many cells are resident and just need to be activated. Since it is known that soluble Neuregulin1 (sNRG1) is released after injury and plays an important role activating Schwann cell dedifferentiation, its expression level was investigated in early regeneration steps (7, 14, 28 days) inside a 10 mm chitosan conduit used to repair median nerve gaps in Wistar rats. In vivo data show that sNRG1, mainly the isoform α, is highly expressed in the conduit, together with a fibroblast marker, while Schwann cell markers, including NRG1 receptors, were not. Primary culture analysis shows that nerve fibroblasts, unlike Schwann cells, express high NRG1α levels, while both express NRG1β. These data suggest that sNRG1 might be mainly expressed by fibroblasts colonizing nerve conduit before Schwann cells. Immunohistochemistry analysis confirmed NRG1 and fibroblast marker co-localization. These results suggest that fibroblasts, releasing sNRG1, might promote Schwann cell dedifferentiation to a “repair” phenotype, contributing to peripheral nerve regeneration.
Keywords: Neuregulin 1; nerve fibroblasts; nerve regeneration; Schwann cells; nerve guide; chitosan; peripheral nerve; nerve repair; nerve injury Neuregulin 1; nerve fibroblasts; nerve regeneration; Schwann cells; nerve guide; chitosan; peripheral nerve; nerve repair; nerve injury

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MDPI and ACS Style

Fornasari, B.E.; El Soury, M.; Nato, G.; Fucini, A.; Carta, G.; Ronchi, G.; Crosio, A.; Perroteau, I.; Geuna, S.; Raimondo, S.; et al. Fibroblasts Colonizing Nerve Conduits Express High Levels of Soluble Neuregulin1, a Factor Promoting Schwann Cell Dedifferentiation. Cells 2020, 9, 1366. https://doi.org/10.3390/cells9061366

AMA Style

Fornasari BE, El Soury M, Nato G, Fucini A, Carta G, Ronchi G, Crosio A, Perroteau I, Geuna S, Raimondo S, et al. Fibroblasts Colonizing Nerve Conduits Express High Levels of Soluble Neuregulin1, a Factor Promoting Schwann Cell Dedifferentiation. Cells. 2020; 9(6):1366. https://doi.org/10.3390/cells9061366

Chicago/Turabian Style

Fornasari, Benedetta E., Marwa El Soury, Giulia Nato, Alessia Fucini, Giacomo Carta, Giulia Ronchi, Alessandro Crosio, Isabelle Perroteau, Stefano Geuna, Stefania Raimondo, and et al. 2020. "Fibroblasts Colonizing Nerve Conduits Express High Levels of Soluble Neuregulin1, a Factor Promoting Schwann Cell Dedifferentiation" Cells 9, no. 6: 1366. https://doi.org/10.3390/cells9061366

APA Style

Fornasari, B. E., El Soury, M., Nato, G., Fucini, A., Carta, G., Ronchi, G., Crosio, A., Perroteau, I., Geuna, S., Raimondo, S., & Gambarotta, G. (2020). Fibroblasts Colonizing Nerve Conduits Express High Levels of Soluble Neuregulin1, a Factor Promoting Schwann Cell Dedifferentiation. Cells, 9(6), 1366. https://doi.org/10.3390/cells9061366

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