PMID- 29042658 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220410 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 IP - 1 DP - 2017 Oct 17 TI - Exosomes secreted by human adipose mesenchymal stem cells promote scarless cutaneous repair by regulating extracellular matrix remodelling. PG - 13321 LID - 10.1038/s41598-017-12919-x [doi] LID - 13321 AB - Scar formation is an intractable medical problem that appears after skin wounds have healed. Recent research has shown that exosomes secreted by human adipose mesenchymal stem cells (ASC-Exos) can benefit wound healing. To further explore the therapeutic potential of ASC-Exos, we investigated their effects on mitigating scar formation, and the underlying mechanisms of these effects. We found that intravenous injection of ASC-Exos decreased the size of scars and increased the ratio of collagen III to collagen I in murine incisional wounds. Exosome treatment also prevented the differentiation of fibroblasts into myofibroblasts and increased the ratio of transforming growth factor-beta3 (TGF-beta3) to TGF-beta1 in vivo. Additionally, we found that ASC-Exos increased the matrix metalloproteinases-3 (MMP3) expression of skin dermal fibroblasts by activating the ERK/MAPK pathway, leading to a high ratio of MMP3 to tissue inhibitor of matrix metalloproteinases-1 (TIMP1), which is also beneficial for the remodelling of extracellular matrix (ECM). In conclusion, our results demonstrated that ASC-Exos promote ECM reconstruction in cutaneous wound repair by regulating the ratios of collagen type III: type I, TGF-beta3:TGF-beta1 and MMP3:TIMP1, and by regulating fibroblast differentiation to mitigate scar formation. Therefore, the application of ASC-Exos may be a novel therapeutic approach for scarless wound repair. FAU - Wang, Lu AU - Wang L AD - Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. FAU - Hu, Li AU - Hu L AD - Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. FAU - Zhou, Xin AU - Zhou X AD - Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. FAU - Xiong, Zehuan AU - Xiong Z AD - Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. FAU - Zhang, Chenguang AU - Zhang C AD - Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. FAU - Shehada, Hassan M A AU - Shehada HMA AD - Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. FAU - Hu, Bo AU - Hu B AD - College of Stomatology, Chongqing Medical University, Chongqing, 401147, P.R. China. FAU - Song, Jinlin AU - Song J AD - College of Stomatology, Chongqing Medical University, Chongqing, 401147, P.R. China. soongjl@163.com. FAU - Chen, Lili AU - Chen L AD - Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. lily-c1030@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171017 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 EIN - Sci Rep. 2018 May 1;8(1):7066. PMID: 29717149 EIN - Sci Rep. 2021 Feb 1;11(1):3245. PMID: 33526797 PMC - PMC5645460 COIS- The authors declare that they have no competing interests. EDAT- 2017/10/19 06:00 MHDA- 2017/10/19 06:01 PMCR- 2017/10/17 CRDT- 2017/10/19 06:00 PHST- 2017/04/26 00:00 [received] PHST- 2017/09/11 00:00 [accepted] PHST- 2017/10/19 06:00 [entrez] PHST- 2017/10/19 06:00 [pubmed] PHST- 2017/10/19 06:01 [medline] PHST- 2017/10/17 00:00 [pmc-release] AID - 10.1038/s41598-017-12919-x [pii] AID - 12919 [pii] AID - 10.1038/s41598-017-12919-x [doi] PST - epublish SO - Sci Rep. 2017 Oct 17;7(1):13321. doi: 10.1038/s41598-017-12919-x.