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Schwann Cell-Derived Exosomes Induce the Differentiation of Human Adipose-Derived Stem Cells Into Schwann Cells

Adipose-derived stem cells (ADSCs) can differentiate into Schwann cells (SCs) at the site of nerve injury, where Schwann cell-derived exosomes (SC-Exos) are suspected to exert an induction effect. Our study aimed to induce the differentiation of ADSCs in vitro using SC-Exos and to investigate the me...

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Autores principales: Zhou, Nan, Xu, Zhao, Li, Xiang, Ren, Sen, Chen, Jing, Xiong, Hewei, Wang, Cheng, Guo, Jiahe, Kang, Yu, Chen, Zhenbing, Li, Wenqing, Yang, Xiaofan, Zhang, Xing, Xu, Xiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8841477/
https://www.ncbi.nlm.nih.gov/pubmed/35174212
http://dx.doi.org/10.3389/fmolb.2021.835135
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author Zhou, Nan
Xu, Zhao
Li, Xiang
Ren, Sen
Chen, Jing
Xiong, Hewei
Wang, Cheng
Guo, Jiahe
Kang, Yu
Chen, Zhenbing
Li, Wenqing
Yang, Xiaofan
Zhang, Xing
Xu, Xiang
author_facet Zhou, Nan
Xu, Zhao
Li, Xiang
Ren, Sen
Chen, Jing
Xiong, Hewei
Wang, Cheng
Guo, Jiahe
Kang, Yu
Chen, Zhenbing
Li, Wenqing
Yang, Xiaofan
Zhang, Xing
Xu, Xiang
author_sort Zhou, Nan
collection PubMed
description Adipose-derived stem cells (ADSCs) can differentiate into Schwann cells (SCs) at the site of nerve injury, where Schwann cell-derived exosomes (SC-Exos) are suspected to exert an induction effect. Our study aimed to induce the differentiation of ADSCs in vitro using SC-Exos and to investigate the mechanisms involved through miRNA sequencing. Subcutaneous fat was used to extract ADSCs. Exosomes were extracted from Schwann cell lines (RSC96) using ultracentrifugation and were able to be taken up by human ADSCs. After 8 days of induction of ADSCs by SC-Exos, phenotypic characteristics were observed by examining the expression of SC markers (S100ß, NGFR, MPZ, GFAP) through RT-qPCR, Western blot and immunofluorescence. The RNA and protein expression levels of S100ß, NGFR, MPZ, and GFAP were found to be significantly higher in the SC-Exo induction group than in the uninduced group, which was also consistent with the immunofluorescence results. Additionally, miRNA sequencing was performed on exosome-induced ADSCs, followed by bioinformatic analysis and validation of the results. According to the sequencing results, there were a total of 94 differentially expressed miRNAs. Bioinformatics analysis indicated that 3506 Gene Ontology terms and 98 Kyoto Encyclopedia of Genes and Genomes pathways were significantly enriched. Ten miRNAs, 5 target mRNAs and elevated expression of the PIK3CD/Akt pathway were validated by RT-qPCR or Western blot, which is consistent with the sequencing results. Our study demonstrates that the utility of SC-Exos is effective in inducing the differentiation of ADSCs into SCs, in which these validated differentially expressed miRNAs exert a vital effect. This work provides a new paradigm via rationally applying Schwann cell-derived exosomes as a promising therapeutic option for repairing peripheral nerve injury.
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spelling pubmed-88414772022-02-15 Schwann Cell-Derived Exosomes Induce the Differentiation of Human Adipose-Derived Stem Cells Into Schwann Cells Zhou, Nan Xu, Zhao Li, Xiang Ren, Sen Chen, Jing Xiong, Hewei Wang, Cheng Guo, Jiahe Kang, Yu Chen, Zhenbing Li, Wenqing Yang, Xiaofan Zhang, Xing Xu, Xiang Front Mol Biosci Molecular Biosciences Adipose-derived stem cells (ADSCs) can differentiate into Schwann cells (SCs) at the site of nerve injury, where Schwann cell-derived exosomes (SC-Exos) are suspected to exert an induction effect. Our study aimed to induce the differentiation of ADSCs in vitro using SC-Exos and to investigate the mechanisms involved through miRNA sequencing. Subcutaneous fat was used to extract ADSCs. Exosomes were extracted from Schwann cell lines (RSC96) using ultracentrifugation and were able to be taken up by human ADSCs. After 8 days of induction of ADSCs by SC-Exos, phenotypic characteristics were observed by examining the expression of SC markers (S100ß, NGFR, MPZ, GFAP) through RT-qPCR, Western blot and immunofluorescence. The RNA and protein expression levels of S100ß, NGFR, MPZ, and GFAP were found to be significantly higher in the SC-Exo induction group than in the uninduced group, which was also consistent with the immunofluorescence results. Additionally, miRNA sequencing was performed on exosome-induced ADSCs, followed by bioinformatic analysis and validation of the results. According to the sequencing results, there were a total of 94 differentially expressed miRNAs. Bioinformatics analysis indicated that 3506 Gene Ontology terms and 98 Kyoto Encyclopedia of Genes and Genomes pathways were significantly enriched. Ten miRNAs, 5 target mRNAs and elevated expression of the PIK3CD/Akt pathway were validated by RT-qPCR or Western blot, which is consistent with the sequencing results. Our study demonstrates that the utility of SC-Exos is effective in inducing the differentiation of ADSCs into SCs, in which these validated differentially expressed miRNAs exert a vital effect. This work provides a new paradigm via rationally applying Schwann cell-derived exosomes as a promising therapeutic option for repairing peripheral nerve injury. Frontiers Media S.A. 2022-01-31 /pmc/articles/PMC8841477/ /pubmed/35174212 http://dx.doi.org/10.3389/fmolb.2021.835135 Text en Copyright © 2022 Zhou, Xu, Li, Ren, Chen, Xiong, Wang, Guo, Kang, Chen, Li, Yang, Zhang and Xu. https://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 Molecular Biosciences
Zhou, Nan
Xu, Zhao
Li, Xiang
Ren, Sen
Chen, Jing
Xiong, Hewei
Wang, Cheng
Guo, Jiahe
Kang, Yu
Chen, Zhenbing
Li, Wenqing
Yang, Xiaofan
Zhang, Xing
Xu, Xiang
Schwann Cell-Derived Exosomes Induce the Differentiation of Human Adipose-Derived Stem Cells Into Schwann Cells
title Schwann Cell-Derived Exosomes Induce the Differentiation of Human Adipose-Derived Stem Cells Into Schwann Cells
title_full Schwann Cell-Derived Exosomes Induce the Differentiation of Human Adipose-Derived Stem Cells Into Schwann Cells
title_fullStr Schwann Cell-Derived Exosomes Induce the Differentiation of Human Adipose-Derived Stem Cells Into Schwann Cells
title_full_unstemmed Schwann Cell-Derived Exosomes Induce the Differentiation of Human Adipose-Derived Stem Cells Into Schwann Cells
title_short Schwann Cell-Derived Exosomes Induce the Differentiation of Human Adipose-Derived Stem Cells Into Schwann Cells
title_sort schwann cell-derived exosomes induce the differentiation of human adipose-derived stem cells into schwann cells
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8841477/
https://www.ncbi.nlm.nih.gov/pubmed/35174212
http://dx.doi.org/10.3389/fmolb.2021.835135
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