PMID- 25824139 OWN - NLM STAT- MEDLINE DCOM- 20150713 LR - 20220408 IS - 2157-6564 (Print) IS - 2157-6580 (Electronic) IS - 2157-6564 (Linking) VI - 4 IP - 5 DP - 2015 May TI - Human umbilical cord mesenchymal stem cell exosomes enhance angiogenesis through the Wnt4/beta-catenin pathway. PG - 513-22 LID - 10.5966/sctm.2014-0267 [doi] AB - Human umbilical cord mesenchymal stem cells (hucMSCs) and their exosomes have been considered as potential therapeutic tools for tissue regeneration; however, the underlying mechanisms are still not well understood. In this study, we isolated and characterized the exosomes from hucMSCs (hucMSC-Ex) and demonstrated that hucMSC-Ex promoted the proliferation, migration, and tube formation of endothelial cells in a dose-dependent manner. Furthermore, we demonstrated that hucMSC-Ex promoted wound healing and angiogenesis in vivo by using a rat skin burn model. We discovered that hucMSC-Ex promoted beta-catenin nuclear translocation and induced the increased expression of proliferating cell nuclear antigen, cyclin D3, N-cadherin, and beta-catenin and the decreased expression of E-cadherin. The activation of Wnt/beta-catenin is critical in the induction of angiogenesis by hucMSC-Ex, which could be reversed by beta-catenin inhibitor ICG-001. Wnt4 was delivered by hucMSC-Ex, and the knockdown of Wnt4 in hucMSC-Ex abrogated beta-catenin nuclear translocation in endothelial cells. The in vivo proangiogenic effects were also inhibited by interference of Wnt4 expression in hucMSC-Ex. Taken together, these results suggest that hucMSC-Ex-mediated Wnt4 induces beta-catenin activation in endothelial cells and exerts proangiogenic effects, which could be an important mechanism for cutaneous wound healing. CI - (c)AlphaMed Press. FAU - Zhang, Bin AU - Zhang B AD - Key Laboratory of Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, Jiangsu University, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China; Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, Jiangsu, People's Republic of China. FAU - Wu, Xiaodan AU - Wu X AD - Key Laboratory of Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, Jiangsu University, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China; Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, Jiangsu, People's Republic of China. FAU - Zhang, Xu AU - Zhang X AD - Key Laboratory of Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, Jiangsu University, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China; Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, Jiangsu, People's Republic of China. FAU - Sun, Yaoxiang AU - Sun Y AD - Key Laboratory of Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, Jiangsu University, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China; Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, Jiangsu, People's Republic of China. FAU - Yan, Yongmin AU - Yan Y AD - Key Laboratory of Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, Jiangsu University, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China; Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, Jiangsu, People's Republic of China. FAU - Shi, Hui AU - Shi H AD - Key Laboratory of Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, Jiangsu University, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China; Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, Jiangsu, People's Republic of China. FAU - Zhu, Yanhua AU - Zhu Y AD - Key Laboratory of Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, Jiangsu University, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China; Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, Jiangsu, People's Republic of China. FAU - Wu, Lijun AU - Wu L AD - Key Laboratory of Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, Jiangsu University, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China; Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, Jiangsu, People's Republic of China. FAU - Pan, Zhaoji AU - Pan Z AD - Key Laboratory of Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, Jiangsu University, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China; Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, Jiangsu, People's Republic of China. FAU - Zhu, Wei AU - Zhu W AD - Key Laboratory of Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, Jiangsu University, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China; Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, Jiangsu, People's Republic of China. FAU - Qian, Hui AU - Qian H AD - Key Laboratory of Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, Jiangsu University, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China; Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, Jiangsu, People's Republic of China icls@ujs.edu.cn lstmmmlst@163.com. FAU - Xu, Wenrong AU - Xu W AD - Key Laboratory of Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, Jiangsu University, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China; Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, Jiangsu, People's Republic of China icls@ujs.edu.cn lstmmmlst@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150330 PL - England TA - Stem Cells Transl Med JT - Stem cells translational medicine JID - 101578022 RN - 0 (Bridged Bicyclo Compounds, Heterocyclic) RN - 0 (ICG 001) RN - 0 (Pyrimidinones) RN - 0 (WNT4 protein, human) RN - 0 (Wnt4 Protein) RN - 0 (beta Catenin) SB - IM MH - Animals MH - Bridged Bicyclo Compounds, Heterocyclic/administration & dosage MH - Endothelial Cells/drug effects/metabolism/transplantation MH - Exosomes/metabolism/transplantation MH - Gene Expression Regulation/drug effects MH - Humans MH - Mesenchymal Stem Cells/cytology MH - *Neovascularization, Physiologic MH - Pyrimidinones/administration & dosage MH - Rats MH - *Regeneration MH - Signal Transduction/drug effects MH - Umbilical Cord/cytology MH - Wnt4 Protein/*biosynthesis MH - *Wound Healing MH - beta Catenin/*biosynthesis PMC - PMC4414225 OTO - NOTNLM OT - Angiogenesis OT - Exosomes OT - Regenerative medicine OT - Wnt4 OT - beta-Catenin EDAT- 2015/04/01 06:00 MHDA- 2015/07/15 06:00 PMCR- 2016/05/01 CRDT- 2015/04/01 06:00 PHST- 2014/11/25 00:00 [received] PHST- 2015/02/02 00:00 [accepted] PHST- 2015/04/01 06:00 [entrez] PHST- 2015/04/01 06:00 [pubmed] PHST- 2015/07/15 06:00 [medline] PHST- 2016/05/01 00:00 [pmc-release] AID - sctm.2014-0267 [pii] AID - 20140267 [pii] AID - 10.5966/sctm.2014-0267 [doi] PST - ppublish SO - Stem Cells Transl Med. 2015 May;4(5):513-22. doi: 10.5966/sctm.2014-0267. Epub 2015 Mar 30.