Characterization of Glial Cell Models andIn VitroManipulation of the Neuregulin1/ErbB System

Abstract

The neuregulin1/ErbB system plays an important role in Schwann cell behavior both in normal and pathological conditions. Upon investigation of the expression of the neuregulin1/ErbB system in vitro, we explored the possibility to manipulate the system in order to increase the migration of Schwann cells, that play a fundamental role in the peripheral nerve regeneration. Comparison of primary cells and stable cell lines shows that both primary olfactory bulb ensheathing cells and a corresponding cell line express ErbB1-ErbB2 and neuregulin1, and that both primary Schwann cells and a corresponding cell line express ErbB2-ErbB3, while only primary Schwann cells express neuregulin1. To interfere with the neuregulin1/ErbB system, the soluble extracellular domain of the neuregulin1 receptor ErbB4 (ecto-ErbB4) was expressed in vitro in the neuregulin1 expressing cell line, and an unexpected increase in cell motility was observed. In vitro experiments suggest that the back signaling mediated by the transmembrane neuregulin1 plays a role in the migratory activity induced by ecto-ErbB4. These results indicate that ecto-ErbB4 could be used in vivo as a tool to manipulate the neuregulin1/ErbB system.

Evaluation of Vascular Endothelial Growth Factor (VEGF) and Its Family Member Expression After Peripheral Nerve Regeneration and Denervation

“…Finally, the cell pellet was resuspended in SC growth medium, seeded into a Petri dish precoated with poly‐ d ‐lysine (Sigma, St Louis, MO), and incubated in the same conditions. SC were purified by an antibody complement method to roll out the remaining fibroblasts (Tohill et al, ; Kaewkhaw et al, ; Pascal et al, ).…”

In vitro models for peripheral nerve regeneration

“…Due to the lack of ethical impact, the use of Schwann cell and nerve cell lines represents the first research step to acquire a body of preliminary data on several basic aspects including: the signalling pathways activated by new molecules/drugs (Armstrong et al ., ; Magnaghi et al ., ; Gnavi et al ., ; Pascal et al ., ); the biocompatibility of new and/or modified biomaterials (Gnavi et al ., ; Novajra et al ., ; Wrobel et al ., ); and the cell behaviour changes due to environmental alterations induced by physical agents (magnetic fields, light radiations, mechanical forces, etc.) (Gamboa et al ., ; Koppes et al ., ; Liu et al ., ). …”

“…Olfactory ensheathing cells share the expression of several specific markers, such as S‐100 and low‐affinity nerve growth factor receptor (p75), with Schwann cells (Guerout et al ., ; Honore et al ., ; Pascal et al ., ). These cells are of particular interest for their ability to promote remyelination of damaged axons in both the central nervous system (Boyd et al ., ) and peripheral nervous system (Guerout et al ., ).…”

“…(i) the signalling pathways activated by new molecules/drugs (Armstrong et al, 2008;Magnaghi et al, 2010;Gnavi et al, 2014;Pascal et al, 2014); (ii) the biocompatibility of new and/or modified biomaterials Novajra et al, 2014;Wrobel et al, 2014); and (iii) the cell behaviour changes due to environmental alterations induced by physical agents (magnetic fields, light radiations, mechanical forces, etc.) (Gamboa et al, 2007;Koppes et al, 2014;Liu et al, 2015).…”

“…However, the expression of the Neuregulin1/ErbB system that characterizes Schwann cell precursor growth and the interactions between Schwann cells (expressing ErbB2-ErbB3 and soluble Neuregulin 1 type I/II) and axons (mainly expressing transmembrane Neuregulin 1, type III), for example, has been found to be different between primary Schwann cells and RT4-D6P2T cells, as the latter do not express Neuregulin 1 type I/II (Pascal et al, 2014).…”