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MSC-derived exosomes attenuate cell death through suppressing AIF nucleus translocation and enhance cutaneous wound healing

BACKGROUND: Skin wounding is very common and may be slow to heal. Increasing evidence shows that exosomes derived from mesenchymal stem cells (MSCs) dramatically enhance skin wound healing in a paracrine manner. However, the mechanism underlying this phenomenon has not yet been elucidated. Thus, the...

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Autores principales: Zhao, Guifang, Liu, Feilin, Liu, Zinan, Zuo, Kuiyang, Wang, Bo, Zhang, Yuying, Han, Xing, Lian, Aobo, Wang, Yuan, Liu, Mingsheng, Zou, Fei, Li, Pengdong, Liu, Xiaomei, Jin, Minghua, Liu, Jin Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212595/
https://www.ncbi.nlm.nih.gov/pubmed/32393338
http://dx.doi.org/10.1186/s13287-020-01616-8
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author Zhao, Guifang
Liu, Feilin
Liu, Zinan
Zuo, Kuiyang
Wang, Bo
Zhang, Yuying
Han, Xing
Lian, Aobo
Wang, Yuan
Liu, Mingsheng
Zou, Fei
Li, Pengdong
Liu, Xiaomei
Jin, Minghua
Liu, Jin Yu
author_facet Zhao, Guifang
Liu, Feilin
Liu, Zinan
Zuo, Kuiyang
Wang, Bo
Zhang, Yuying
Han, Xing
Lian, Aobo
Wang, Yuan
Liu, Mingsheng
Zou, Fei
Li, Pengdong
Liu, Xiaomei
Jin, Minghua
Liu, Jin Yu
author_sort Zhao, Guifang
collection PubMed
description BACKGROUND: Skin wounding is very common and may be slow to heal. Increasing evidence shows that exosomes derived from mesenchymal stem cells (MSCs) dramatically enhance skin wound healing in a paracrine manner. However, the mechanism underlying this phenomenon has not yet been elucidated. Thus, the objective of the present study was to identify the signaling pathways and paracrine factors by which MSC-derived exosomes promote de novo skin tissue regeneration in response to wound healing. METHODS: In vitro and in vivo skin wound healing models were created by treating immortalized human keratinocytes (HaCaT) with hydrogen peroxide (H(2)O(2)) and excising full-thickness mouse skin, respectively. Exosomes were extracted from human umbilical cord Wharton’s jelly MSCs (hucMSC-Ex) by ultracentrifugation of cell culture supernatant. RESULTS: The hucMSC-Ex treatment significantly increased HaCaT cell proliferation and migration in a time- and dose-dependent manner, suppressed HaCaT apoptosis induced with H(2)O(2) by inhibiting nuclear translocation of apoptosis-inducing factor (AIF) and upregulating poly ADP ribose polymerase 1 (PARP-1) and poly (ADP-ribose) (PAR). The animal experiments showed that relative to hucMSCs, hucMSC-Ex attenuated full-thickness skin wounding by enhancing epidermal re-epithelialization and dermal angiogenesis. CONCLUSIONS: These findings indicated that direct administration of hucMSC-Ex may effectively treat cutaneous wounding and could be of great value in clinical settings.
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spelling pubmed-72125952020-05-18 MSC-derived exosomes attenuate cell death through suppressing AIF nucleus translocation and enhance cutaneous wound healing Zhao, Guifang Liu, Feilin Liu, Zinan Zuo, Kuiyang Wang, Bo Zhang, Yuying Han, Xing Lian, Aobo Wang, Yuan Liu, Mingsheng Zou, Fei Li, Pengdong Liu, Xiaomei Jin, Minghua Liu, Jin Yu Stem Cell Res Ther Research BACKGROUND: Skin wounding is very common and may be slow to heal. Increasing evidence shows that exosomes derived from mesenchymal stem cells (MSCs) dramatically enhance skin wound healing in a paracrine manner. However, the mechanism underlying this phenomenon has not yet been elucidated. Thus, the objective of the present study was to identify the signaling pathways and paracrine factors by which MSC-derived exosomes promote de novo skin tissue regeneration in response to wound healing. METHODS: In vitro and in vivo skin wound healing models were created by treating immortalized human keratinocytes (HaCaT) with hydrogen peroxide (H(2)O(2)) and excising full-thickness mouse skin, respectively. Exosomes were extracted from human umbilical cord Wharton’s jelly MSCs (hucMSC-Ex) by ultracentrifugation of cell culture supernatant. RESULTS: The hucMSC-Ex treatment significantly increased HaCaT cell proliferation and migration in a time- and dose-dependent manner, suppressed HaCaT apoptosis induced with H(2)O(2) by inhibiting nuclear translocation of apoptosis-inducing factor (AIF) and upregulating poly ADP ribose polymerase 1 (PARP-1) and poly (ADP-ribose) (PAR). The animal experiments showed that relative to hucMSCs, hucMSC-Ex attenuated full-thickness skin wounding by enhancing epidermal re-epithelialization and dermal angiogenesis. CONCLUSIONS: These findings indicated that direct administration of hucMSC-Ex may effectively treat cutaneous wounding and could be of great value in clinical settings. BioMed Central 2020-05-11 /pmc/articles/PMC7212595/ /pubmed/32393338 http://dx.doi.org/10.1186/s13287-020-01616-8 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zhao, Guifang
Liu, Feilin
Liu, Zinan
Zuo, Kuiyang
Wang, Bo
Zhang, Yuying
Han, Xing
Lian, Aobo
Wang, Yuan
Liu, Mingsheng
Zou, Fei
Li, Pengdong
Liu, Xiaomei
Jin, Minghua
Liu, Jin Yu
MSC-derived exosomes attenuate cell death through suppressing AIF nucleus translocation and enhance cutaneous wound healing
title MSC-derived exosomes attenuate cell death through suppressing AIF nucleus translocation and enhance cutaneous wound healing
title_full MSC-derived exosomes attenuate cell death through suppressing AIF nucleus translocation and enhance cutaneous wound healing
title_fullStr MSC-derived exosomes attenuate cell death through suppressing AIF nucleus translocation and enhance cutaneous wound healing
title_full_unstemmed MSC-derived exosomes attenuate cell death through suppressing AIF nucleus translocation and enhance cutaneous wound healing
title_short MSC-derived exosomes attenuate cell death through suppressing AIF nucleus translocation and enhance cutaneous wound healing
title_sort msc-derived exosomes attenuate cell death through suppressing aif nucleus translocation and enhance cutaneous wound healing
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212595/
https://www.ncbi.nlm.nih.gov/pubmed/32393338
http://dx.doi.org/10.1186/s13287-020-01616-8
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