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

Abstract

BackgroundThe 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.MethodsWe 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.ResultsWe 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.ConclusionsBlue (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

Mesenchymal Stem Cell-Derived Exosomes: Biological Function and Their Therapeutic Potential in Radiation Damage

“…In addition to such bioactive substances, environmental factors impact the proangiogenic properties of MSC-exosomes. In fact, exposure of MSCs to blue light resulted in the increased content of miRNA-135b-5p and miRNA-499a-3p as exosomal cargo, which promoted angiogenesis in vitro by repressing myocyte enhancer factor 2C (MEF2C) [66]. Consistent with this finding, hypoxia enhanced the cargo content of miRNA-126 in MSC-exosomes.…”

Extracellular vesicles derived from different sources of mesenchymal stem cells: therapeutic effects and translational potential

“…Under blue light exposure, HuC-MSC-Ex can promote angiogenesis in vivo and enhance its ability to promote angiogenesis. It was confirmed that the exosomes treated by blue light stimulated the activation of endothelial cells by upregulating the two miRNAs of mir-135b-5p and mir-499a-3p [79].…”

<p>Umbilical Cord-Derived Mesenchymal Stem Cell-Derived Exosomes Combined Pluronic F127 Hydrogel Promote Chronic Diabetic Wound Healing and Complete Skin Regeneration</p>

“…Yang et al showed that blue light exposure could elevated levels of miR-135b-5p and miR-499a-3p to increased proangiogenic capacity in MSC-exos. 63 Therapy based on photon energy has been broadly recommended as a method to accelerate diabetic wound healing. A future strategy for wound management might involve a noninvasive, economical, and multipurpose lightdependent cellular treatment.…”