PMID- 31779691 OWN - NLM STAT- MEDLINE DCOM- 20200724 LR - 20200724 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 10 IP - 1 DP - 2019 Nov 28 TI - Exposure to blue light stimulates the proangiogenic capability of exosomes derived from human umbilical cord mesenchymal stem cells. PG - 358 LID - 10.1186/s13287-019-1472-x [doi] LID - 358 AB - BACKGROUND: The therapeutic potential of mesenchymal stem cells (MSCs) may be attributed partly to the secreted paracrine factors, which comprise exosomes. Exosomes are small, saucer-shaped vesicles containing miRNAs, mRNAs, and proteins. Exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) have been reported to promote angiogenesis. However, the efficacy of exosome-based therapies is still limited both in vitro and in vivo. The present study aimed to develop a new optical manipulation approach to stimulate the proangiogenic potential of exosomes and characterize its mechanism underlying tissue regeneration. METHODS: We used blue (455 nm) and red (638 nm) monochromatic light exposure to investigate the processing of stimuli. Exosomes were prepared by QIAGEN exoEasy Maxi kit and confirmed to be present by transmission electron microscopy and immunoblotting analyses. The proangiogenic activity of blue light-treated human umbilical vein endothelial cells (HUVECs), when co-cultured with hUC-MSCs, was assessed by EdU (5-ethynyl-2'-deoxyuridine) incorporation, wound closure, and endothelial tube formation assays. The in vivo angiogenic activity of blue light-treated MSC-derived exosomes (MSC-Exs) was evaluated using both murine matrigel plug and skin wound models. RESULTS: We found that 455-nm blue light is effective for promoting proliferation, migration, and tube formation of HUVECs co-cultured with MSCs. Furthermore, MSC-Exs stimulated in vivo angiogenesis and their proangiogenic potential were enhanced significantly upon blue light illumination. Finally, activation of the endothelial cells in response to stimulation by blue light-treated exosomes was demonstrated by upregulation of two miRNAs, miR-135b-5p, and miR-499a-3p. CONCLUSIONS: Blue (455 nm) light illumination improved the therapeutic effects of hUC-MSC exosomes by enhancing their proangiogenic ability in vitro and in vivo with the upregulation of the following two miRNAs: miR-135b-5p and miR-499a-3p. FAU - Yang, Kun AU - Yang K AD - Key Laboratory of Experimental Teratology, Ministry of Education Department of Medical Genetics, School of Basic Medical Sciences, Shandong University, 44 Wen Hua Xi Road, Jinan, Shandong, 250012, People's Republic of China. FAU - Li, Dong AU - Li D AD - Cryomedicine Laboratory, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China. AD - Stem Cell and Regenerative Medicine Research Center of Shandong University, Jinan, 250012, Shandong, China. FAU - Wang, Meitian AU - Wang M AD - Key Laboratory of Experimental Teratology, Ministry of Education Department of Medical Genetics, School of Basic Medical Sciences, Shandong University, 44 Wen Hua Xi Road, Jinan, Shandong, 250012, People's Republic of China. FAU - Xu, Zhiliang AU - Xu Z AD - Key Laboratory of Experimental Teratology, Ministry of Education Department of Medical Genetics, School of Basic Medical Sciences, Shandong University, 44 Wen Hua Xi Road, Jinan, Shandong, 250012, People's Republic of China. FAU - Chen, Xiao AU - Chen X AD - Key Laboratory of Experimental Teratology, Ministry of Education Department of Medical Genetics, School of Basic Medical Sciences, Shandong University, 44 Wen Hua Xi Road, Jinan, Shandong, 250012, People's Republic of China. FAU - Liu, Qiao AU - Liu Q AD - Key Laboratory of Experimental Teratology, Ministry of Education Department of Medical Genetics, School of Basic Medical Sciences, Shandong University, 44 Wen Hua Xi Road, Jinan, Shandong, 250012, People's Republic of China. FAU - Sun, Wenjie AU - Sun W AD - Key Laboratory of Experimental Teratology, Ministry of Education Department of Medical Genetics, School of Basic Medical Sciences, Shandong University, 44 Wen Hua Xi Road, Jinan, Shandong, 250012, People's Republic of China. FAU - Li, Jiangxia AU - Li J AD - Key Laboratory of Experimental Teratology, Ministry of Education Department of Medical Genetics, School of Basic Medical Sciences, Shandong University, 44 Wen Hua Xi Road, Jinan, Shandong, 250012, People's Republic of China. FAU - Gong, Yaoqin AU - Gong Y AD - Key Laboratory of Experimental Teratology, Ministry of Education Department of Medical Genetics, School of Basic Medical Sciences, Shandong University, 44 Wen Hua Xi Road, Jinan, Shandong, 250012, People's Republic of China. FAU - Liu, Duo AU - Liu D AD - State Key Laboratory of Crystal Materials, Shandong University, Jinan, Shandong, 250100, People's Republic of China. FAU - Shao, Changshun AU - Shao C AD - The First Affiliated Hospital of Soochow University and State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University, Suzhou, 215123, Jiangsu, China. FAU - Liu, Qiji AU - Liu Q AD - Key Laboratory of Experimental Teratology, Ministry of Education Department of Medical Genetics, School of Basic Medical Sciences, Shandong University, 44 Wen Hua Xi Road, Jinan, Shandong, 250012, People's Republic of China. FAU - Li, Xi AU - Li X AUID- ORCID: 0000-0003-2912-5803 AD - Key Laboratory of Experimental Teratology, Ministry of Education Department of Medical Genetics, School of Basic Medical Sciences, Shandong University, 44 Wen Hua Xi Road, Jinan, Shandong, 250012, People's Republic of China. lixi@sdu.edu.cn. AD - Advanced Medical Research Institute, Shandong University, Jinan, 250012, Shandong, China. lixi@sdu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191128 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - 0 (MicroRNAs) SB - IM MH - Animals MH - Burns/pathology/therapy MH - Cell Movement/radiation effects MH - Cell Proliferation/radiation effects MH - Cells, Cultured MH - Coculture Techniques MH - Disease Models, Animal MH - Exosomes/metabolism/*radiation effects/transplantation MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - *Light MH - Male MH - Mesenchymal Stem Cells/cytology/metabolism MH - Mice MH - Mice, Inbred C57BL MH - MicroRNAs/metabolism MH - Neovascularization, Physiologic/*radiation effects MH - Umbilical Cord/cytology MH - Up-Regulation/radiation effects PMC - PMC6883639 OTO - NOTNLM OT - Angiogenesis OT - Exosomes OT - Light exposure OT - Mesenchymal stem cells OT - microRNAs COIS- The authors declare that they have no competing interests. EDAT- 2019/11/30 06:00 MHDA- 2020/07/25 06:00 PMCR- 2019/11/28 CRDT- 2019/11/30 06:00 PHST- 2019/07/11 00:00 [received] PHST- 2019/10/28 00:00 [accepted] PHST- 2019/09/20 00:00 [revised] PHST- 2019/11/30 06:00 [entrez] PHST- 2019/11/30 06:00 [pubmed] PHST- 2020/07/25 06:00 [medline] PHST- 2019/11/28 00:00 [pmc-release] AID - 10.1186/s13287-019-1472-x [pii] AID - 1472 [pii] AID - 10.1186/s13287-019-1472-x [doi] PST - epublish SO - Stem Cell Res Ther. 2019 Nov 28;10(1):358. doi: 10.1186/s13287-019-1472-x.