MSC-derived exosomes attenuate cell death through suppressing AIF nucleus translocation and enhance cutaneous wound healing
Abstract 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. T...
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| Format: | Article |
| Language: | English |
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BMC
2020-05-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | http://link.springer.com/article/10.1186/s13287-020-01616-8 |
| _version_ | 1828518683378450432 |
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| author | Guifang Zhao Feilin Liu Zinan Liu Kuiyang Zuo Bo Wang Yuying Zhang Xing Han Aobo Lian Yuan Wang Mingsheng Liu Fei Zou Pengdong Li Xiaomei Liu Minghua Jin Jin Yu Liu |
| author_facet | Guifang Zhao Feilin Liu Zinan Liu Kuiyang Zuo Bo Wang Yuying Zhang Xing Han Aobo Lian Yuan Wang Mingsheng Liu Fei Zou Pengdong Li Xiaomei Liu Minghua Jin Jin Yu Liu |
| author_sort | Guifang Zhao |
| collection | DOAJ |
| description | Abstract 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 (H2O2) 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 H2O2 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. |
| first_indexed | 2024-12-11T18:58:45Z |
| format | Article |
| id | doaj.art-8750e5885eda4027b1f6dea1ffbda43b |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-11T18:58:45Z |
| publishDate | 2020-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-8750e5885eda4027b1f6dea1ffbda43b2022-12-22T00:54:03ZengBMCStem Cell Research & Therapy1757-65122020-05-0111111810.1186/s13287-020-01616-8MSC-derived exosomes attenuate cell death through suppressing AIF nucleus translocation and enhance cutaneous wound healingGuifang Zhao0Feilin Liu1Zinan Liu2Kuiyang Zuo3Bo Wang4Yuying Zhang5Xing Han6Aobo Lian7Yuan Wang8Mingsheng Liu9Fei Zou10Pengdong Li11Xiaomei Liu12Minghua Jin13Jin Yu Liu14Department of Toxicology, School of Public Health, Jilin UniversityDepartment of Ophthalmology, the Second Hospital of Jilin UniversityDepartment of Toxicology, School of Public Health, Jilin UniversityDepartment of Toxicology, School of Public Health, Jilin UniversityDepartment of Toxicology, School of Public Health, Jilin UniversityDepartment of Toxicology, School of Public Health, Jilin UniversityDepartment of Toxicology, School of Public Health, Jilin UniversityDepartment of Toxicology, School of Public Health, Jilin UniversityDepartment of Toxicology, School of Public Health, Jilin UniversityDepartment of Toxicology, School of Public Health, Jilin UniversityDepartment of Toxicology, School of Public Health, Jilin UniversityDepartment of Toxicology, School of Public Health, Jilin UniversityDepartment of Toxicology, School of Public Health, Jilin UniversityDepartment of Toxicology, School of Public Health, Jilin UniversityDepartment of Toxicology, School of Public Health, Jilin UniversityAbstract 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 (H2O2) 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 H2O2 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.http://link.springer.com/article/10.1186/s13287-020-01616-8ApoptosisApoptosis-inducing factorExosomesMesenchymal stem cellsPoly (ADP-ribose) polymerase-1Protease-activated receptor |
| spellingShingle | Guifang Zhao Feilin Liu Zinan Liu Kuiyang Zuo Bo Wang Yuying Zhang Xing Han Aobo Lian Yuan Wang Mingsheng Liu Fei Zou Pengdong Li Xiaomei Liu Minghua Jin Jin Yu Liu MSC-derived exosomes attenuate cell death through suppressing AIF nucleus translocation and enhance cutaneous wound healing Stem Cell Research & Therapy Apoptosis Apoptosis-inducing factor Exosomes Mesenchymal stem cells Poly (ADP-ribose) polymerase-1 Protease-activated receptor |
| 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 | Apoptosis Apoptosis-inducing factor Exosomes Mesenchymal stem cells Poly (ADP-ribose) polymerase-1 Protease-activated receptor |
| url | http://link.springer.com/article/10.1186/s13287-020-01616-8 |
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