Exposure to blue light stimulates the proangiogenic capability of exosomes derived from human umbilical cord mesenchymal stem cells

• DOI: 10.1186/s13287-019-1472-x
• Publication Date: 2019-11-28T16:02:47Z
• Authors: Kun Yang; Dong Li; Meitian Wang; Zhiliang Xu; Xiao Chen; Qiao Liu; Wenjie Sun; Jiangxia Li; Yaoqin Gong; Duo Liu; Changshun Shao; Qiji Liu; Xi Li
• Keywords: Male; 0301 basic medicine; Medicine (General); Light; Neovascularization, Physiologic; QD415-436; Exosomes; Biochemistry; Umbilical Cord; Mice; 03 medical and health sciences; R5-920; Cell Movement; Human Umbilical Vein Endothelial Cells; Animals; Humans; Cells, Cultured; Cell Proliferation; Research; Light exposure; Mesenchymal Stem Cells; Coculture Techniques; microRNAs; Up-Regulation; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; MicroRNAs; Mesenchymal stem cells; Angiogenesis; Burns

Abstract 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.

Graphical abstract