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A Novel Experimental Model to Determine the Axon-Promoting Effects of Grafted Cells After Peripheral Nerve Injury

Although peripheral nerves can regenerate, clinical outcomes after peripheral nerve injuries are not always satisfactory, especially in cases of severe or proximal injuries. Further, autologous nerve grafting remains the gold standard for the reconstruction of peripheral nerves, although this method...

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Autores principales: Endo, Takeshi, Kadoya, Ken, Suzuki, Yuki, Kawamura, Daisuke, Iwasaki, Norimasa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611175/
https://www.ncbi.nlm.nih.gov/pubmed/31316351
http://dx.doi.org/10.3389/fncel.2019.00280
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author Endo, Takeshi
Kadoya, Ken
Suzuki, Yuki
Kawamura, Daisuke
Iwasaki, Norimasa
author_facet Endo, Takeshi
Kadoya, Ken
Suzuki, Yuki
Kawamura, Daisuke
Iwasaki, Norimasa
author_sort Endo, Takeshi
collection PubMed
description Although peripheral nerves can regenerate, clinical outcomes after peripheral nerve injuries are not always satisfactory, especially in cases of severe or proximal injuries. Further, autologous nerve grafting remains the gold standard for the reconstruction of peripheral nerves, although this method is still accompanied by issues of donor-site morbidity and limited supply. Cell therapy is a potential approach to overcome these issues. However, the optimal cell type for promoting axon regeneration remains unknown. Here, we report a novel experimental model dedicated to elucidation of the axon-promoting effects of candidate cell types using simple and standardized techniques. This model uses rat sciatic nerves and consists of a 25 mm-long acellular region and a crush site at each end. The acellular region was made by repeated freeze/thaw procedures with liquid nitrogen. Importantly, the new model does not require microsurgical procedures, which are technically demanding and greatly affect axon regeneration. To test the actual utility of this model, red fluorescent protein-expressing syngeneic Schwann cells (SCs), marrow stromal cells, or fibroblasts were grafted into the acellular area, followed by perfusion of the rat 2 weeks later. All types of grafted cells survived well. Quantification of regenerating axons demonstrated that SCs, but not the other cell types, promoted axon regeneration with minimum variability. Thus, this model is useful for differentiating the effects of various grafted cell types in axon regeneration. Interestingly, regardless of the grafted cell type, host SCs migrated into the acellular area, and the extent of axon regeneration was strongly correlated with the number of SCs. Moreover, all regenerating axons were closely associated with SCs. These findings suggest a critical role for SCs in peripheral nerve axon regeneration. Collectively, this novel experimental model is useful for elucidating the axon-promoting effects of grafted cells and for analyzing the biology of peripheral nerve axon regeneration.
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spelling pubmed-66111752019-07-17 A Novel Experimental Model to Determine the Axon-Promoting Effects of Grafted Cells After Peripheral Nerve Injury Endo, Takeshi Kadoya, Ken Suzuki, Yuki Kawamura, Daisuke Iwasaki, Norimasa Front Cell Neurosci Neuroscience Although peripheral nerves can regenerate, clinical outcomes after peripheral nerve injuries are not always satisfactory, especially in cases of severe or proximal injuries. Further, autologous nerve grafting remains the gold standard for the reconstruction of peripheral nerves, although this method is still accompanied by issues of donor-site morbidity and limited supply. Cell therapy is a potential approach to overcome these issues. However, the optimal cell type for promoting axon regeneration remains unknown. Here, we report a novel experimental model dedicated to elucidation of the axon-promoting effects of candidate cell types using simple and standardized techniques. This model uses rat sciatic nerves and consists of a 25 mm-long acellular region and a crush site at each end. The acellular region was made by repeated freeze/thaw procedures with liquid nitrogen. Importantly, the new model does not require microsurgical procedures, which are technically demanding and greatly affect axon regeneration. To test the actual utility of this model, red fluorescent protein-expressing syngeneic Schwann cells (SCs), marrow stromal cells, or fibroblasts were grafted into the acellular area, followed by perfusion of the rat 2 weeks later. All types of grafted cells survived well. Quantification of regenerating axons demonstrated that SCs, but not the other cell types, promoted axon regeneration with minimum variability. Thus, this model is useful for differentiating the effects of various grafted cell types in axon regeneration. Interestingly, regardless of the grafted cell type, host SCs migrated into the acellular area, and the extent of axon regeneration was strongly correlated with the number of SCs. Moreover, all regenerating axons were closely associated with SCs. These findings suggest a critical role for SCs in peripheral nerve axon regeneration. Collectively, this novel experimental model is useful for elucidating the axon-promoting effects of grafted cells and for analyzing the biology of peripheral nerve axon regeneration. Frontiers Media S.A. 2019-06-28 /pmc/articles/PMC6611175/ /pubmed/31316351 http://dx.doi.org/10.3389/fncel.2019.00280 Text en Copyright © 2019 Endo, Kadoya, Suzuki, Kawamura and Iwasaki. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Endo, Takeshi
Kadoya, Ken
Suzuki, Yuki
Kawamura, Daisuke
Iwasaki, Norimasa
A Novel Experimental Model to Determine the Axon-Promoting Effects of Grafted Cells After Peripheral Nerve Injury
title A Novel Experimental Model to Determine the Axon-Promoting Effects of Grafted Cells After Peripheral Nerve Injury
title_full A Novel Experimental Model to Determine the Axon-Promoting Effects of Grafted Cells After Peripheral Nerve Injury
title_fullStr A Novel Experimental Model to Determine the Axon-Promoting Effects of Grafted Cells After Peripheral Nerve Injury
title_full_unstemmed A Novel Experimental Model to Determine the Axon-Promoting Effects of Grafted Cells After Peripheral Nerve Injury
title_short A Novel Experimental Model to Determine the Axon-Promoting Effects of Grafted Cells After Peripheral Nerve Injury
title_sort novel experimental model to determine the axon-promoting effects of grafted cells after peripheral nerve injury
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611175/
https://www.ncbi.nlm.nih.gov/pubmed/31316351
http://dx.doi.org/10.3389/fncel.2019.00280
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