Resorbable Structures for Schwann Cell Enhanced Peripheral Nerve Regeneration

1998 ◽  
Vol 550 ◽  
Author(s):  
A.E. Silva ◽  
LC. Summerhayes ◽  
D.J. Trantolo ◽  
D.L. Wise ◽  
M.V. Catftaneo ◽  
...  

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.


Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1366 ◽  
Author(s):  
Benedetta E. Fornasari ◽  
Marwa El Soury ◽  
Giulia Nato ◽  
Alessia Fucini ◽  
Giacomo Carta ◽  
...  

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.



2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Hongkui Wang ◽  
Ping Zhang ◽  
Jun Yu ◽  
Fuchao Zhang ◽  
Wenzhao Dai ◽  
...  

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.



1999 ◽  
Vol 160 (1) ◽  
pp. 99-108 ◽  
Author(s):  
Kojun Torigoe ◽  
Kazuo Hashimoto ◽  
Göran Lundborg


1989 ◽  
Vol 83 (6) ◽  
pp. 1020-1021 ◽  
Author(s):  
Peter G. Cordeiro ◽  
Brooke R. Seckel ◽  
Stuart A. Lipton ◽  
Patricia A. DʼAmore ◽  
John Wagner ◽  
...  


2021 ◽  
Vol 14 ◽  
Author(s):  
Bo Jia ◽  
Wei Huang ◽  
Yu Wang ◽  
Peng Zhang ◽  
Zhiwei Wang ◽  
...  

While Nogo protein demonstrably inhibits nerve regeneration in the central nervous system (CNS), its effect on Schwann cells in peripheral nerve repair and regeneration following sciatic nerve injury remains unknown. In this research, We assessed the post-injury expression of Nogo-C in an experimental mouse model of sciatic nerve-crush injury. Nogo-C knockout (Nogo-C–/–) mouse was generated to observe the effect of Nogo-C on sciatic nerve regeneration, Schwann cell apoptosis, and myelin disintegration after nerve injury, and the effects of Nogo-C on apoptosis and dedifferentiation of Schwann cells were observed in vitro. We found that the expression of Nogo-C protein at the distal end of the injured sciatic nerve increased in wild type (WT) mice. Compared with the injured WT mice, the proportion of neuronal apoptosis was significantly diminished and the myelin clearance rate was significantly elevated in injured Nogo-C–/– mice; the number of nerve fibers regenerated and the degree of myelination were significantly elevated in Nogo-C–/– mice on Day 14 after injury. In addition, the recovery of motor function was significantly accelerated in the injured Nogo-C–/– mice. The overexpression of Nogo-C in primary Schwann cells using adenovirus-mediated gene transfer promoted Schwann cells apoptosis. Nogo-C significantly reduced the ratio of c-Jun/krox-20 expression, indicating its inhibition of Schwann cell dedifferentiation. Above all, we hold the view that the expression of Nogo-C increases following peripheral nerve injury to promote Schwann cell apoptosis and inhibit Schwann cell dedifferentiation, thereby inhibiting peripheral nerve regeneration.



2000 ◽  
Vol 6 (2) ◽  
pp. 129-138 ◽  
Author(s):  
David J. Bryan ◽  
Antonia H. Holway ◽  
Kai-Kai Wang ◽  
Alyson E. Silva ◽  
Debra J. Trantolo ◽  
...  




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