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Hypocapnia Stimuli-Responsive Engineered Exosomes Delivering miR-218 Facilitate Sciatic Nerve Regeneration

Therapeutic strategies of microRNAs (miRNAs) and exosomes have been systematically explored as an enhancing application by paracrine and modulating cellular activity after internalization of recipient cells in vitro, and progressively developed to meet the requirements of peripheral nerve regenerati...

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Autores principales: Wang, Yingshuai, Yu, Tao, Hu, Feihu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861458/
https://www.ncbi.nlm.nih.gov/pubmed/35211463
http://dx.doi.org/10.3389/fbioe.2022.825146
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author Wang, Yingshuai
Yu, Tao
Hu, Feihu
author_facet Wang, Yingshuai
Yu, Tao
Hu, Feihu
author_sort Wang, Yingshuai
collection PubMed
description Therapeutic strategies of microRNAs (miRNAs) and exosomes have been systematically explored as an enhancing application by paracrine and modulating cellular activity after internalization of recipient cells in vitro, and progressively developed to meet the requirements of peripheral nerve regeneration in vivo. However, how to obtain exosomes with superior properties and effectively deliver miRNAs becomes a key challenge. Hypocapnia environment might play unexpected outcomes in strengthening exosome function when culturing adipose-derived stem cells (ASCs). Previously, we discovered the intensive regulation of miR-218 on the differentiation of ASCs. In the present study, we analyzed the functional differences of secreted exosomes in response to hypocapnia stimulation, and explored the application in combination with miR-218 to facilitate sciatic nerve regeneration. Our results indicated that the delivery system of engineered exosomes derived from ASCs remarkably loads upregulated miR-218 and promotes cellular activity in the recipient cells (PC12 cells), and hypocapnia stimuli-responsive exosomes exhibit strengthening properties. Furthermore, in a sciatic nerve injury model, exosomes delivering miR-218 combined with engineered scaffold facilitated the regeneration of injured sciatic nerves. In the hypocapnia-stimulated exosome group, more encouraging promotion was revealed on the regeneration of motor and nerve fibers. Hypoc-miR-218-ASC exosomes are suggested as a promising cell-free strategy for peripheral nerve repair.
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spelling pubmed-88614582022-02-23 Hypocapnia Stimuli-Responsive Engineered Exosomes Delivering miR-218 Facilitate Sciatic Nerve Regeneration Wang, Yingshuai Yu, Tao Hu, Feihu Front Bioeng Biotechnol Bioengineering and Biotechnology Therapeutic strategies of microRNAs (miRNAs) and exosomes have been systematically explored as an enhancing application by paracrine and modulating cellular activity after internalization of recipient cells in vitro, and progressively developed to meet the requirements of peripheral nerve regeneration in vivo. However, how to obtain exosomes with superior properties and effectively deliver miRNAs becomes a key challenge. Hypocapnia environment might play unexpected outcomes in strengthening exosome function when culturing adipose-derived stem cells (ASCs). Previously, we discovered the intensive regulation of miR-218 on the differentiation of ASCs. In the present study, we analyzed the functional differences of secreted exosomes in response to hypocapnia stimulation, and explored the application in combination with miR-218 to facilitate sciatic nerve regeneration. Our results indicated that the delivery system of engineered exosomes derived from ASCs remarkably loads upregulated miR-218 and promotes cellular activity in the recipient cells (PC12 cells), and hypocapnia stimuli-responsive exosomes exhibit strengthening properties. Furthermore, in a sciatic nerve injury model, exosomes delivering miR-218 combined with engineered scaffold facilitated the regeneration of injured sciatic nerves. In the hypocapnia-stimulated exosome group, more encouraging promotion was revealed on the regeneration of motor and nerve fibers. Hypoc-miR-218-ASC exosomes are suggested as a promising cell-free strategy for peripheral nerve repair. Frontiers Media S.A. 2022-02-08 /pmc/articles/PMC8861458/ /pubmed/35211463 http://dx.doi.org/10.3389/fbioe.2022.825146 Text en Copyright © 2022 Wang, Yu and Hu. 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 Bioengineering and Biotechnology
Wang, Yingshuai
Yu, Tao
Hu, Feihu
Hypocapnia Stimuli-Responsive Engineered Exosomes Delivering miR-218 Facilitate Sciatic Nerve Regeneration
title Hypocapnia Stimuli-Responsive Engineered Exosomes Delivering miR-218 Facilitate Sciatic Nerve Regeneration
title_full Hypocapnia Stimuli-Responsive Engineered Exosomes Delivering miR-218 Facilitate Sciatic Nerve Regeneration
title_fullStr Hypocapnia Stimuli-Responsive Engineered Exosomes Delivering miR-218 Facilitate Sciatic Nerve Regeneration
title_full_unstemmed Hypocapnia Stimuli-Responsive Engineered Exosomes Delivering miR-218 Facilitate Sciatic Nerve Regeneration
title_short Hypocapnia Stimuli-Responsive Engineered Exosomes Delivering miR-218 Facilitate Sciatic Nerve Regeneration
title_sort hypocapnia stimuli-responsive engineered exosomes delivering mir-218 facilitate sciatic nerve regeneration
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861458/
https://www.ncbi.nlm.nih.gov/pubmed/35211463
http://dx.doi.org/10.3389/fbioe.2022.825146
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