Enhanced proangiogenic potential of mesenchymal stem cell-derived exosomes stimulated by a nitric oxide releasing polymer
Enhanced proangiogenic potential of mesenchymal stem cell-derived exosomes stimulated by a nitric oxide releasing polymer
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一氧化氮释放聚合物刺激间充质干细胞来源的外泌体增强促血管生成潜力
DOI：
10.1016/j.biomaterials.2017.04.030
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发表时间：
2017-07-01
期刊：
影响因子：
14
通讯作者：
Li, Zongjin
中科院分区：
文献类型：
--
作者：
Du, Wei;Zhang, Kaiyue;Li, Zongjin
间充质干细胞（MSC）衍生的外泌体已被认为是治疗退行性疾病或损伤的新候选者，并可能提供细胞基础治疗的替代方案。然而，msc来源的外泌体的组成受到其原始细胞所在微环境的高度影响。在这里，我们假设一氧化氮（NO）释放聚合物可以提高外泌体的促血管生成成分并增强其促血管生成能力。我们的研究结果表明，通过NO刺激从人胎盘源性间充质干细胞（hP-MSCs）中释放的外泌体增强了体外人脐静脉内皮细胞（HUVECs）的血管生成作用。此外，通过NO刺激hP-MSCs释放的外泌体在小鼠后肢缺血模型中显示出优越的血管生成作用和改善的肢体功能。进一步的分析表明，通过NO刺激hP-MSCs释放的外泌体中VEGF和miR-126水平的增加被确定为促进这些外泌体促进血管生成过程能力增加的新机制。总之，为体外干细胞培养设计特定的微环境，例如那些含有生物活性物质的微环境，将有助于开发定制的外泌体，包封干细胞的有益成分，用于无细胞治疗应用。(C) 2017 Elsevier Ltd.版权所有。
Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidates for the treatment of degenerative diseases or injury and may provide an alternative to cell-based therapy. However, the compositions in MSC-derived exosomes are highly influenced by the microenvironment in which their original cells reside. Here, we hypothesized that a nitric oxide (NO)-releasing polymer can boost the proangiogenic compositions of exosomes and enhance their proangiogenic capacity. Our results demonstrated that exosomes, released from human placenta-derived MSCs (hP-MSCs) by NO stimulation, augment the angiogenic effects of human umbilical vein endothelial cells (HUVECs) in vitro. Moreover, exosomes released from hP-MSCs by NO stimulation revealed superior angiogenic effects and ameliorated limb function in a murine model of hind limb ischemia. Further analysis demonstrated that increased VEGF and miR-126 levels in exosomes released from hP-MSCs by NO stimulation were identified as a novel mechanism contributing to the increased capacity of these exosomes to promote angiogenic processes. In conclusion, designing specific microenvironments for in vitro stem cell culture, such as those containing bioactive material, will facilitate the development of customized exosomes encapsulating a beneficial composition of stem cells for cell-free therapeutic applications. (C) 2017 Elsevier Ltd. All rights reserved.