Doxorubicin-Immersed Skeletal Muscle Grafts Promote Peripheral Nerve Regeneration Across a 10-mm Defect in the Rat Sciatic Nerve

2019 ◽  
Vol 36 (01) ◽  
pp. 041-052
Author(s):  
Hisataka Takeuchi ◽  
Akio Sakamoto ◽  
Ryosuke Ikeguchi ◽  
Soichi Ota ◽  
Hiroki Oda ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Muscle Atrophy ◽  
Rat Model ◽  
Axonal Regeneration ◽  
Peripheral Nerve Regeneration ◽  
Group Versus ◽  
Nerve Autograft

Background The treatment of peripheral nerve defects requires bridging materials. Skeletal muscle grafts have been studied as an alternative to nerve autografts because they contain longitudinally aligned basal laminar tubes that are similar to axons. Several pretreatment methods for muscle grafts have promoted axonal regeneration. Here, a new method of doxorubicin pretreatment was used, and the efficacy of the pretreated muscle graft was evaluated in a rat model of a sciatic nerve defect. Methods A rat model of a 10-mm sciatic nerve defect was analyzed in three settings: muscle grafts with and without doxorubicin pretreatment (M-graft-w-Dox and M-graft-w/o-Dox groups, respectively) and a nerve autograft group (N-graft) (n = 6/group). The M-graft-w-Dox group was immersed in a doxorubicin solution for 10 minutes and rinsed with saline. Analyses of target muscle atrophy, electrophysiology, and histology were performed 8 weeks after grafting. Results Electrophysiological parameters and target muscle atrophy were significantly superior in the M-graft-w-Dox group compared with the M-graft-w/o-Dox group. Histological assessment revealed the presence of a significantly greater number of regenerated axons in the M-graft-w-Dox group versus the M-graft-w/o-Dox group, while there were no significant differences between the M-graft-w-Dox and N-graft groups. The diameter of myelinated axons of the regenerated nerve in the M-graft-w-Dox group was significantly larger than that in the M-graft-w/o-Dox group, while it was not significantly different compared with the N-graft group. Conclusion Pretreatment of muscle grafts with doxorubicin promoted significant peripheral nerve regeneration. This method may represent a new option for the treatment of peripheral nerve defects.

scholarly journals Peripheral Nerve Regeneration Using a Cytokine Cocktail Secreted by Skeletal Muscle-Derived Stem Cells in a Mouse Model

2021 ◽  
Vol 10 (4) ◽  
pp. 824
Author(s):  
Daisuke Maki ◽  
Tetsuro Tamaki ◽  
Tsuyoshi Fukuzawa ◽  
Toshiharu Natsume ◽  
Ippei Yamato ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Peripheral Nerve Regeneration ◽  
Mouse Serum ◽  
Facilitation Effect ◽  
Myelinated Fibers ◽  
Cytokine Cocktail

Severe peripheral nerve injury, which does not promise natural healing, inevitably requires clinical treatment. Here, we demonstrated the facilitation effect of peripheral nerve regeneration using a cytokine cocktail secreted by skeletal muscle-derived stem cells (Sk-MSCs). Mouse sciatic nerve was transected with a 6 mm gap and bridged collagen tube, and the culture supernatant of Sk-MSCs with 20% adult mouse serum (AMS)/Iscove’s modified Dulbecco’s medium (IMDM) was administered into the tube immediately after the operation, followed by an injection once a week for six weeks through the skin to the surrounding tube of the cytokine (CT) group. Similarly, 20% AMS/IMDM without cytokines was administered to the non-cytokine control (NT) group. Tension recovery in the plantar flexor muscles via electrical stimulation at the upper portion of the damaged nerve site, as well as the numerical recovery of axons and myelinated fibers at the damaged site, were evaluated as an index of nerve regeneration. Specific cytokines secreted by Sk-MSCs were compared with damaged sciatic nerve-derived cytokines. Six weeks after operation, significantly higher tension output and numerical recovery of the axon and myelinated fibers were consistently observed in the CT group, showing that the present cytokine cocktail may be a useful nerve regeneration acceleration agent. We also determined 17 candidate factors, which are likely included in the cocktail.

scholarly journals Carbon-nanotube yarns induce axonal regeneration in peripheral nerve defect

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Atsushi Kunisaki ◽  
Akira Kodama ◽  
Masakazu Ishikawa ◽  
Takahiro Ueda ◽  
Marcio D. Lima ◽  
...  
Keyword(s):  
Carbon Nanotube ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Axonal Regeneration ◽  
Peripheral Nerve Regeneration ◽  
Weight Ratio ◽  
Muscle Weight ◽  
Gait Function ◽  
Carbon Nanotube Yarns

AbstractCarbon nanotubes (CNTs) are cylindrical nanostructures and have unique properties, including flexibility, electrical conductivity, and biocompatibility. We focused on CNTs fabricated with the carbon nanotube yarns (cYarn) as a possible substrate promoting peripheral nerve regeneration with these properties. We bridged a 15 mm rat sciatic nerve defect with five different densities of cYarn. Eight weeks after the surgery, the regenerated axons crossing the CNTs, electromyographical findings, and muscle weight ratio of the lower leg showed recovery of the nerve function by interfacing with cYarn. Furthermore, the sciatic nerve functional index (SFI) at 16 weeks showed improvement in gait function. A 2% CNT density tended to be the most effective for nerve regeneration as measured by both histological axonal regeneration and motor function. We confirmed that CNT yarn promotes peripheral nerve regeneration by using it as a scaffold for repairing nerve defects. Our results support the future clinical application of CNTs for bridging nerve defects as an off-the-shelf material.

scholarly journals IL-17F depletion accelerates chitosan conduit guided peripheral nerve regeneration

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Feixiang Chen ◽  
Weihuang Liu ◽  
Qiang Zhang ◽  
Ping Wu ◽  
Ao Xiao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Knockout Mice ◽  
Inflammatory Markers ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Wild Type ◽  
Anti Inflammatory

AbstractPeripheral nerve injury is a serious health problem and repairing long nerve deficits remains a clinical challenge nowadays. Nerve guidance conduit (NGC) serves as the most promising alternative therapy strategy to autografts but its repairing efficiency needs improvement. In this study, we investigated whether modulating the immune microenvironment by Interleukin-17F (IL-17F) could promote NGC mediated peripheral nerve repair. Chitosan conduits were used to bridge sciatic nerve defect in IL-17F knockout mice and wild-type mice with autografts as controls. Our data revealed that IL-17F knockout mice had improved functional recovery and axonal regeneration of sciatic nerve bridged by chitosan conduits comparing to the wild-type mice. Notably, IL-17F knockout mice had enhanced anti-inflammatory macrophages in the NGC repairing microenvironment. In vitro data revealed that IL-17F knockout peritoneal and bone marrow derived macrophages had increased anti-inflammatory markers after treatment with the extracts from chitosan conduits, while higher pro-inflammatory markers were detected in the Raw264.7 macrophage cell line, wild-type peritoneal and bone marrow derived macrophages after the same treatment. The biased anti-inflammatory phenotype of macrophages by IL-17F knockout probably contributed to the improved chitosan conduit guided sciatic nerve regeneration. Additionally, IL-17F could enhance pro-inflammatory factors production in Raw264.7 cells and wild-type peritoneal macrophages. Altogether, IL-17F may partially mediate chitosan conduit induced pro-inflammatory polarization of macrophages during nerve repair. These results not only revealed a role of IL-17F in macrophage function, but also provided a unique and promising target, IL-17F, to modulate the microenvironment and enhance the peripheral nerve regeneration.

scholarly journals Histopathological analysis of gangliosides use in peripheral nerve regeneration after axonotmesis in rats

2008 ◽  
Vol 23 (4) ◽  
pp. 364-371 ◽  
Author(s):  
Camila Maria Beder Ribeiro ◽  
Belmiro Cavalcanti do Egito Vasconcelos ◽  
Joaquim Celestino da Silva Neto ◽  
Valdemiro Amaro da Silva Júnior ◽  
Nancy Gurgel Figueiredo
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Peripheral Nerve Regeneration ◽  
Cell Activity ◽  
Control Group ◽  
Histopathological Analysis ◽  
Male Wistar Rats ◽  
The Right

PURPOSE: To analyze the action of gangliosides in peripheral nerve regeneration in the sciatic nerve of the rat. METHODS: The sample was composed of 96 male Wistar rats. The animals were anaesthetized and, after identification of the anaesthesic plane, an incision was made in the posterior region of the thigh, followed by skin and muscle divulsion. The right sciatic nerve was isolated and compressed for 2 minutes. Continuous suture of the skin was performed. The animals were randomly divided into two groups: the experimental group (EG), which received subcutaneous injection of gangliosides, and the control group (CG), which received saline solution (0.9%) to mimic the effects of drug administration. RESULTS: No differences were observed between the experimental and control groups evaluated on the eighth day of observation. At 15 and 30 days the EG showed an decrease in Schwann cell activity and an apparent improvement in fibre organization; at 60 days, there was a slight presence of Schwann cells in the endoneural space and the fibres were organized, indicating nerve regeneration. At 15 and 30 days, the level of cell reaction in the CG had diminished, but there were many cells with cytoplasm in activity and in mitosis; at 60 days, hyperplastic Schwann cells and mitotic activity were again observed, as well as nerve regeneration, but to a lesser extent than in the EG. CONCLUSION: The administration of exogenous gangliosides seems to improve nerve regeneration.

scholarly journals Gellan Gum-based luminal fillers for peripheral nerve regeneration: an in vivo study in the rat sciatic nerve repair model

2018 ◽  
Vol 6 (5) ◽  
pp. 1059-1075 ◽  
Author(s):  
C. R. Carvalho ◽  
S. Wrobel ◽  
C. Meyer ◽  
C. Brandenberger ◽  
I. F. Cengiz ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Experimental Work ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Gellan Gum ◽  
In Vivo Study ◽  
Rat Sciatic Nerve

This experimental work considers the innovative use of the biomaterial Gellan Gum (GG) as a luminal filler for nerve guidance channels.

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