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Enhanced Nerve Regeneration by Exosomes Secreted by Adipose-Derived Stem Cells with or without FK506 Stimulation

Exosomes secreted by adipose-derived stem cells (ADSC-exo) reportedly improve nerve regeneration after peripheral nerve injury. Herein, we investigated whether pretreatment of ADSCs with FK506, an immunosuppressive drug that enhances nerve regeneration, could secret exosomes (ADSC-F-exo) that furthe...

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Autores principales: Rau, Cheng-Shyuan, Kuo, Pao-Jen, Wu, Shao-Chun, Huang, Lien-Hung, Lu, Tsu-Hsiang, Wu, Yi-Chan, Wu, Chia-Jung, Lin, Chia-Wei, Tsai, Chia-Wen, Hsieh, Ching-Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395161/
https://www.ncbi.nlm.nih.gov/pubmed/34445251
http://dx.doi.org/10.3390/ijms22168545
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author Rau, Cheng-Shyuan
Kuo, Pao-Jen
Wu, Shao-Chun
Huang, Lien-Hung
Lu, Tsu-Hsiang
Wu, Yi-Chan
Wu, Chia-Jung
Lin, Chia-Wei
Tsai, Chia-Wen
Hsieh, Ching-Hua
author_facet Rau, Cheng-Shyuan
Kuo, Pao-Jen
Wu, Shao-Chun
Huang, Lien-Hung
Lu, Tsu-Hsiang
Wu, Yi-Chan
Wu, Chia-Jung
Lin, Chia-Wei
Tsai, Chia-Wen
Hsieh, Ching-Hua
author_sort Rau, Cheng-Shyuan
collection PubMed
description Exosomes secreted by adipose-derived stem cells (ADSC-exo) reportedly improve nerve regeneration after peripheral nerve injury. Herein, we investigated whether pretreatment of ADSCs with FK506, an immunosuppressive drug that enhances nerve regeneration, could secret exosomes (ADSC-F-exo) that further augment nerve regeneration. Designed exosomes were topically applied to injured nerve in a mouse model of sciatic nerve crush injury to assess the nerve regeneration efficacy. Outcomes were determined by histomorphometric analysis of semi-thin nerve sections stained with toluidine blue, mouse neurogenesis PCR array, and neurotrophin expression in distal nerve segments. Isobaric tags for relative and absolute quantitation (iTRAQ) were used to profile potential exosomal proteins facilitating nerve regeneration. We observed that locally applied ADSC-exo and ADSC-F-exo significantly enhanced nerve regeneration after nerve crush injury. Pretreatment of ADSCs with FK506 failed to produce exosomes possessing more potent molecules for enhanced nerve regeneration. Proteomic analysis revealed that of 192 exosomal proteins detected in both ADSC-exo and ADSC-F-exo, histone deacetylases (HDACs), amyloid-beta A4 protein (APP), and integrin beta-1 (ITGB1) might be involved in enhancing nerve regeneration.
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spelling pubmed-83951612021-08-28 Enhanced Nerve Regeneration by Exosomes Secreted by Adipose-Derived Stem Cells with or without FK506 Stimulation Rau, Cheng-Shyuan Kuo, Pao-Jen Wu, Shao-Chun Huang, Lien-Hung Lu, Tsu-Hsiang Wu, Yi-Chan Wu, Chia-Jung Lin, Chia-Wei Tsai, Chia-Wen Hsieh, Ching-Hua Int J Mol Sci Article Exosomes secreted by adipose-derived stem cells (ADSC-exo) reportedly improve nerve regeneration after peripheral nerve injury. Herein, we investigated whether pretreatment of ADSCs with FK506, an immunosuppressive drug that enhances nerve regeneration, could secret exosomes (ADSC-F-exo) that further augment nerve regeneration. Designed exosomes were topically applied to injured nerve in a mouse model of sciatic nerve crush injury to assess the nerve regeneration efficacy. Outcomes were determined by histomorphometric analysis of semi-thin nerve sections stained with toluidine blue, mouse neurogenesis PCR array, and neurotrophin expression in distal nerve segments. Isobaric tags for relative and absolute quantitation (iTRAQ) were used to profile potential exosomal proteins facilitating nerve regeneration. We observed that locally applied ADSC-exo and ADSC-F-exo significantly enhanced nerve regeneration after nerve crush injury. Pretreatment of ADSCs with FK506 failed to produce exosomes possessing more potent molecules for enhanced nerve regeneration. Proteomic analysis revealed that of 192 exosomal proteins detected in both ADSC-exo and ADSC-F-exo, histone deacetylases (HDACs), amyloid-beta A4 protein (APP), and integrin beta-1 (ITGB1) might be involved in enhancing nerve regeneration. MDPI 2021-08-09 /pmc/articles/PMC8395161/ /pubmed/34445251 http://dx.doi.org/10.3390/ijms22168545 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rau, Cheng-Shyuan
Kuo, Pao-Jen
Wu, Shao-Chun
Huang, Lien-Hung
Lu, Tsu-Hsiang
Wu, Yi-Chan
Wu, Chia-Jung
Lin, Chia-Wei
Tsai, Chia-Wen
Hsieh, Ching-Hua
Enhanced Nerve Regeneration by Exosomes Secreted by Adipose-Derived Stem Cells with or without FK506 Stimulation
title Enhanced Nerve Regeneration by Exosomes Secreted by Adipose-Derived Stem Cells with or without FK506 Stimulation
title_full Enhanced Nerve Regeneration by Exosomes Secreted by Adipose-Derived Stem Cells with or without FK506 Stimulation
title_fullStr Enhanced Nerve Regeneration by Exosomes Secreted by Adipose-Derived Stem Cells with or without FK506 Stimulation
title_full_unstemmed Enhanced Nerve Regeneration by Exosomes Secreted by Adipose-Derived Stem Cells with or without FK506 Stimulation
title_short Enhanced Nerve Regeneration by Exosomes Secreted by Adipose-Derived Stem Cells with or without FK506 Stimulation
title_sort enhanced nerve regeneration by exosomes secreted by adipose-derived stem cells with or without fk506 stimulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395161/
https://www.ncbi.nlm.nih.gov/pubmed/34445251
http://dx.doi.org/10.3390/ijms22168545
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