A Central Role for the ERK-Signaling Pathway in Controlling Schwann Cell Plasticity and Peripheral Nerve Regeneration In Vivo

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.

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Schwann Cell Plasticity in Peripheral Nerve Regeneration after Injury

10.5772/intechopen.91805 ◽

2020 ◽

Author(s):

Emilia Manole ◽

Alexandra Eugenia Bastian ◽

Ana Maria Oproiu ◽

Monica Teodora Neagu ◽

Carolina Constantin ◽

...

Keyword(s):

Schwann Cell ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Peripheral Nerve Regeneration ◽

Cell Plasticity

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Transforming growth factor-? and forskolin attenuate the adverse effects of long-term Schwann cell denervation on peripheral nerve regeneration in vivo

Glia ◽

10.1002/glia.10022 ◽

2002 ◽

Vol 37 (3) ◽

pp. 206-218 ◽

Cited By ~ 64

Author(s):

Olawale A.R. Sulaiman ◽

Tessa Gordon

Keyword(s):

Growth Factor ◽

Adverse Effects ◽

Schwann Cell ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Transforming Growth Factor ◽

Peripheral Nerve Regeneration

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Human Hair Derived Keratins Mediate Schwann Cell Behavior in vitro and Facilitate Rapid Peripheral Nerve Regeneration in vivo

The FASEB Journal ◽

10.1096/fasebj.21.6.a1273-d ◽

2007 ◽

Vol 21 (6) ◽

Author(s):

Paulina Sierpinski ◽

Jeffrey Garrett ◽

Jianjun Ma ◽

Peter Apel ◽

Tom Smith ◽

...

Keyword(s):

Schwann Cell ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Human Hair ◽

Peripheral Nerve Regeneration ◽

Cell Behavior

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Matrix metalloproteinase 7 promoted Schwann cell migration and myelination after rat sciatic nerve injury

Molecular Brain ◽

10.1186/s13041-019-0516-6 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 4

Author(s):

Hongkui Wang ◽

Ping Zhang ◽

Jun Yu ◽

Fuchao Zhang ◽

Wenzhao Dai ◽

...

Keyword(s):

Cell Migration ◽

Sciatic Nerve ◽

Schwann Cell ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Schwann Cells ◽

Nerve Injury ◽

Peripheral Nerve Regeneration ◽

Schwann Cell Migration

AbstractSchwann cells experience de-differentiation, proliferation, migration, re-differentiation and myelination, and participate in the repair and regeneration of injured peripheral nerves. Our previous sequencing analysis suggested that the gene expression level of matrix metalloproteinase 7 (MMP7), a Schwann cell-secreted proteolytic enzyme, was robustly elevated in rat sciatic nerve segments after nerve injury. However, the biological roles of MMP7 are poorly understood. Here, we exposed primary cultured Schwann cells with MMP7 recombinant protein and transfected siRNA against MMP7 into Schwann cells to examine the effect of exogenous and endogenous MMP7. Meanwhile, the effects of MMP7 in nerve regeneration after sciatic nerve crush in vivo were observed. Furthermore, RNA sequencing and bioinformatic analysis of Schwann cells were conducted to show the molecular mechanism behind the phenomenon. In vitro studies showed that MMP7 significantly elevated the migration rate of Schwann cells but did not affect the proliferation rate of Schwann cells. In vivo studies demonstrated that increased level of MMP7 contributed to Schwann cell migration and myelin sheaths formation after peripheral nerve injury. MMP7-mediated genetic changes were revealed by sequencing and bioinformatic analysis. Taken together, our current study demonstrated the promoting effect of MMP7 on Schwann cell migration and peripheral nerve regeneration, benefited the understanding of cellular and molecular mechanisms underlying peripheral nerve injury, and thus might facilitate the treatment of peripheral nerve regeneration in clinic.

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Resorbable Structures for Schwann Cell Enhanced Peripheral Nerve Regeneration

MRS Proceedings ◽

10.1557/proc-550-297 ◽

1998 ◽

Vol 550 ◽

Cited By ~ 1

Author(s):

A.E. Silva ◽

LC. Summerhayes ◽

D.J. Trantolo ◽

D.L. Wise ◽

M.V. Catftaneo ◽

...

Keyword(s):

Growth Factor ◽

Schwann Cell ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Schwann Cells ◽

Peripheral Nerve Regeneration ◽

Cell Movement ◽

Regenerative Process

AbstractSchwann cells play a dual role serving as a physical framework for regenerating nerves, providing extracellular matrix proteins and specific adhesion molecules facilitating attachment and cell movement, and as a source of stimulatory factors mediated by the release or reception of different ligands important in growth and cell signaling events. To investigate the role of one such ligand, glial growth factor (GGF), in peripheral nerve regeneration, a bioabsorbable nerve guide, prepared from a poly(lactic-co-glycolic) acid (PLGA) foam was seeded with autogenous Schwann cells in the presence and absence of growth factor and evaluated in vivo using a rat sciatic nerve regeneration model. Four weeks post-operatively peripheral nerve regeneration was evident. The resorbable foam implant demonstrated extensive neo-vascularization in and around the guide with no evidence of an inflammatory response or encapsulation. The study showed a statistically significant increase in all measured parameters of nerve regeneration in the presence of GGF. Increased numbers of blood vessels in the regenerated tissue accompanied increased total axon counts after twelve weeks. The addition of exogenous Schwann cells resulted in reduced total axon counts perhaps due to the competition for limited growth factors released by the regenerating tissues. The Schwann cell groups, however, displayed the highest myelination indices recorded likely reflecting the role of Schwann cells in the myelination process. Measurements of conduction velocities (EMGs) revealed the highest conductance velocities recorded in nerves regenerated in the presence of both GGF and Schwann cells. Clearly, the inclusion of GGF in the nerve regenerative process is beneficial with respect to both the generation of new axons and the establishment of a functional endpoint.

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