PMID- 32611371 OWN - NLM STAT- MEDLINE DCOM- 20210618 LR - 20210618 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 11 IP - 1 DP - 2020 Jul 1 TI - Extracellular vesicles from adipose-derived stem cells ameliorate ultraviolet B-induced skin photoaging by attenuating reactive oxygen species production and inflammation. PG - 264 LID - 10.1186/s13287-020-01777-6 [doi] LID - 264 AB - BACKGROUND: Large numbers of adipose-derived stem cells (ADSCs) are easily obtained and have been demonstrated to protect against ultraviolet B (UVB)-induced skin photoaging. Extracellular vesicles (EVs) exhibit some of the same effects as the cells from which they originate and have many advantages over stem cells. In particular, their application circumvents many safety concerns associated with cell therapy. Thus, as a cell-free agent, adipose-derived stem cell extracellular vesicles (ADSC-EVs) have anti-photoaging potential. However, the protective effects of ADSC-EVs in skin photoaging remain uncertain. METHODS: To investigate the effect of ADSC-EVs on mice with UVB-induced photoaging, 150 mug and 300 mug ADSC-EVs were subcutaneously injected weekly into photoaging mice for 8 weeks. The protective effect was evaluated by gross assessment and hematoxylin and eosin, Masson's trichrome, and beta-galactosidase staining. Proliferating cell nuclear antigen, CD68, and dihydroethidium staining were performed to evaluate cell proliferation, inflammation infiltration, and reactive oxygen species (ROS) production, respectively. In vitro, 100 mug/mL and 200 mug/mL ADSC-EVs were used to treat photoaging fibroblasts (FBs). beta-galactosidase staining and collagen 1 and matrix metalloproteinase 3 (MMP-3) expression were analyzed to evaluate FB senescence. To explain the protective mechanism of ADSC-EVs, their role in regulating ROS production, antioxidant enzyme expression, cell cycle arrest, and inflammation was evaluated. RESULTS: In vivo, we showed that ADSC-EVs decreased skin wrinkles in mice with UVB-induced photoaging, while promoting epidermal cell proliferation and attenuating macrophage infiltration and ROS production. In vitro, we showed that ADSC-EVs increased FB activity and protected FBs from UVB-induced senescence, attenuated raw 264.7 cell differentiation from M0 to M1 macrophages, reduced intracellular ROS production, promoted antioxidant enzyme expression, and rescued FBs from cell cycle arrest. CONCLUSION: The anti-photoaging effect of ADSC-EVs was attributed to their ability to attenuate ROS production and the inflammatory response, which are key factors in MMP activation and collagen degradation. FAU - Xu, Peng AU - Xu P AD - Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. FAU - Xin, Yu AU - Xin Y AD - Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. FAU - Zhang, Zheng AU - Zhang Z AD - Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. FAU - Zou, Xiangyu AU - Zou X AD - Department of Urology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China. FAU - Xue, Ke AU - Xue K AD - Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. FAU - Zhang, Huizhong AU - Zhang H AD - Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. FAU - Zhang, Wenjie AU - Zhang W AD - Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. FAU - Liu, Kai AU - Liu K AD - Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. prskailiu@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200701 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - 0 (Reactive Oxygen Species) SB - IM MH - Animals MH - *Extracellular Vesicles MH - Fibroblasts MH - Inflammation MH - Mice MH - Reactive Oxygen Species MH - Skin MH - *Skin Aging MH - Stem Cells MH - Ultraviolet Rays/adverse effects PMC - PMC7329484 OTO - NOTNLM OT - Adipose-derived stem cells OT - Extracellular vesicles OT - Inflammation OT - Photoaging OT - ROS COIS- The authors declare that they have no competing interests. EDAT- 2020/07/03 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/07/01 CRDT- 2020/07/03 06:00 PHST- 2020/03/22 00:00 [received] PHST- 2020/06/17 00:00 [accepted] PHST- 2020/05/20 00:00 [revised] PHST- 2020/07/03 06:00 [entrez] PHST- 2020/07/03 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/07/01 00:00 [pmc-release] AID - 10.1186/s13287-020-01777-6 [pii] AID - 1777 [pii] AID - 10.1186/s13287-020-01777-6 [doi] PST - epublish SO - Stem Cell Res Ther. 2020 Jul 1;11(1):264. doi: 10.1186/s13287-020-01777-6.