Exposure to blue light stimulates the proangiogenic capability of exosomes derived from human umbilical cord mesenchymal stem cells
Exposure to blue light stimulates the proangiogenic capability of exosomes derived from human umbilical cord mesenchymal stem cells
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暴露于蓝光会刺激源自人脐带间充质干细胞的外泌体的促血管生成能力
DOI：
10.1186/s13287-019-1472-x
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发表时间：
2019-11-28
影响因子：
7.5
通讯作者：
Li, Xi
中科院分区：
文献类型：
--
作者：
Yang, Kun;Li, Dong;Li, Xi
背景间充质干细胞(MSCs)的治疗潜力可能部分归因于分泌的旁分泌因子，而这些旁分泌因子是由外体组成的。外切体是含有miRNAs、mRNAs和蛋白质的碟形小泡。人脐带间充质干细胞(Huc-MSCs)来源的外体具有促进血管生成的作用。然而，基于外切体的疗法在体外和体内的疗效仍然有限。本研究旨在开发一种新的光学操作方法来激发外切体的血管前生成潜力，并表征其组织再生的机制。方法采用蓝光(455 Nm)和红光(638 Nm)单色光照射，研究刺激的加工过程。用QIAGEN exoEasy Maxi试剂盒制备外切体，经透射电子显微镜和免疫印迹分析证实存在外切体。用EDU(5-乙炔-2‘-脱氧尿嘧啶核苷)掺入法、伤口闭合试验和内皮管形成试验检测蓝光处理的人脐静脉内皮细胞(HUVECs)与Huc-MSCs共培养后的促血管生成活性。用小鼠基质塞和皮肤创伤模型评价蓝光处理的MSC来源的外切体(MSC-Exs)的体内血管生成活性。结果发现455 nm蓝光能有效促进人脐静脉内皮细胞与间充质干细胞共培养的增殖、迁移和管状形成。此外，在蓝光照射下，MSC-Exs刺激的体内血管生成及其促血管生成的能力显著增强。最后，通过上调两个miRNAs，miR-135B-5P和miR-499A-3P，证明了内皮细胞对蓝光处理的外切体刺激的激活。结论455 nm蓝光照射可通过上调miR-135B-5p和miR-499a-3p两种miRNAs的表达，增强Huc-MSC外切体的体内外促血管生成能力，从而提高其治疗效果。
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.