DPSCs seeded in acellular nerve grafts processed by Myroilysin improve nerve regeneration

Since synthetic nerve conduits do not exhibit ideal regeneration characteristics, they are generally inadequate substitutes for autologous nerve grafts in the repair of long peripheral nerve defects. To resolve this problem, in this study, a nerve regeneration acellular nerve graft (ANG) with homologous dental pulp stem cells (DPSCs) was constructed. Xenogeneic ANG was processed by Myroilysin to completely remove cells and myelin sheath, while preserving extracellular matrix (ECM) microstructure of the natural nerve. The study revealed that ANG could support cell attachment and proliferation and did not stimulate a vigorous host rejection response. After inoculation of rabbit DPSCs (r-DPSCs) onto ANG, cells were observed to align along the longitudinal axis of the acellular nerve matrix (ANM) and persistently express NGF and BDNF. Undifferentiated r-DPSCs also presented glial cell characteristics and promoted nerve regeneration after transplantation in vivo. We repaired 1 cm purebred New Zealand White Rabbits sciatic nerve defects using this nerve graft construction, and nerve gap regeneration was indicated by electrophysiological and histological analysis. Therefore, we conclude that the combination of an ANG processed by Myroilysin with DPSCs providing a microenvironment that increases nerve regeneration for repairing peripheral nerve defects.

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

Cells ◽

10.3390/cells9061366 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1366 ◽

Cited By ~ 1

Author(s):

Benedetta E. Fornasari ◽

Marwa El Soury ◽

Giulia Nato ◽

Alessia Fucini ◽

Giacomo Carta ◽

...

Keyword(s):

Schwann Cell ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Schwann Cells ◽

Peripheral Nerve Regeneration ◽

Good Alternative ◽

Cell Dedifferentiation ◽

Nerve Conduits ◽

Early Regeneration

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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Single-Lumen and Multi-Lumen Poly(Ethylene Glycol) Nerve Conduits Fabricated by Stereolithography for Peripheral Nerve Regeneration In Vivo

Journal of Reconstructive Microsurgery ◽

10.1055/s-0034-1395415 ◽

2015 ◽

Vol 31 (05) ◽

pp. 327-335 ◽

Cited By ~ 17

Author(s):

Mireya Perez ◽

Ara Salibian ◽

Jeffrey Hassan ◽

Sean Darcy ◽

Keyianoosh Paydar ◽

...

Keyword(s):

Ethylene Glycol ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Peripheral Nerve Regeneration ◽

Poly Ethylene Glycol ◽

Single Lumen ◽

Nerve Conduits ◽

Poly Ethylene

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Development of Multi-channel Electro-conductive Nanofibrous Conduits for Peripheral Nerve Regeneration

10.21203/rs.3.rs-367393/v1 ◽

2021 ◽

Author(s):

Niloofar Nazeri ◽

Mohammad Ali Derakhshan ◽

Korosh Mansoori ◽

Hossein Ghanbari

Keyword(s):

Peripheral Nerve ◽

Nerve Regeneration ◽

Cell Attachment ◽

Peripheral Nerve Regeneration ◽

Nerve Fibers ◽

Cross Sectional ◽

Nerve Conduits ◽

Mean Diameter ◽

Sciatic Nerve Regeneration

Abstract Multichannel structures in the design of nerve conduits offer potential advantages for regeneration of damaged nerves due to their bio-mimicking architecture. However, lack of biochemical cues and electrical stimulation could hamper satisfactory nerve regeneration. The aim of this study was to simultaneously evaluate the effects of topographical, biological and electrical cues on sciatic nerve regeneration in a rat model. Accordingly, a series of multichannel nanofibrous nerve conduit was made using longitudinally-aligned laminin-coated electrospun PLGA/CNT nanofibers (NF, mean diameter: 455 ± 362 nm) in the lumen and randomly-oriented PCL NF (mean diameter: 340 ± 200 nm) on the outer surface. In vitro studies revealed that both materials were nontoxic to Schwann cells and able to promote cell attachment and proliferation. To determine the influence of topographical, biological and electrical cues on nerve regeneration, either of hollow PCL conduits, PLGA NF-embedded, PLGA/CNT NF-embedded or laminin-coated PLGA/CNT NF-embedded PCL conduits were implanted in rats. A new surgery method was utilized and results were compared with an autograft. After animal treatments, motor and sensory tests showed significant improvement in the rats treated with NF-embedded PCL conduits. H&E images obtained from cross-sectional and, longitudinal-sections of the regenerated nerves demonstrated the formation of regenerative nerve fibers and also, angiogenesis in laminin-coated PLGA/CNT NF-embedded PCL conduits. Results suggested that these conduits have the potential for clinical application to reconstruct peripheral nerve defects.

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