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.

Fibroblasts colonizing nerve conduits express high levels of soluble Neuregulin1, a factor promoting Schwann cell dedifferentiation

Benedetta E. Fornasari
First
;
Marwa El Soury;Giulia Nato;Giacomo Carta;Giulia Ronchi;Alessandro Crosio;Isabelle Perroteau;Stefano Geuna;Stefania Raimondo;Giovanna Gambarotta
Last
2020

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.
9
-
1366
1384
Neuregulin 1; nerve fibroblasts; nerve regeneration; Schwann cells; nerve guide; chitosan; peripheral nerve; nerve repair; nerve injury
Benedetta E. Fornasari, Marwa El Soury, Giulia Nato, Alessia Fucini, Giacomo Carta, Giulia Ronchi, Alessandro Crosio, Isabelle Perroteau, Stefano Geuna, Stefania Raimondo, Giovanna Gambarotta
File in questo prodotto:
File Dimensione Formato  
Fornasari_Cells_2020.pdf

Accesso aperto

Descrizione: Articolo principale
Tipo di file: PDF EDITORIALE
Dimensione 3.79 MB
Formato Adobe PDF
3.79 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1740156
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 5
  • ???jsp.display-item.citation.isi??? 7
social impact