MSC-derived exosomes attenuate cell death through suppressing AIF nucleus translocation and enhance cutaneous wound healing
Open Access
- 11 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Stem Cell Research & Therapy
- Vol. 11 (1), 1-18
- https://doi.org/10.1186/s13287-020-01616-8
Abstract
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. 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. 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. These findings indicated that direct administration of hucMSC-Ex may effectively treat cutaneous wounding and could be of great value in clinical settings.Keywords
Funding Information
- China Natural National Science Foundation (81573067, 81901972)
- the Joint construction project between Jilin province and provincial colleges (SXGJQY2017-12)
- Jilin Province Science and technology development plan (20190304044YY)
- Innovative special industry fund project in Jilin province (2018C049-2)
- the Open Research Project of the State Key Laboratory of Industrial Control Technology, Zhejiang University, China (ICT1800381)
- ilin Province Department of Education (JJKH20191063KJ)
- Jilin City Science and Technology Innovation Development Plan Project (201831745)
- ilin Medical College Doctoral Research Foundation Project (JYBS2018011)
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