The Kinetics of Small Extracellular Vesicle Delivery Impacts Skin Tissue Regeneration
The Kinetics of Small Extracellular Vesicle Delivery Impacts Skin Tissue Regeneration
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DOI：
10.1021/acsnano.9b00376
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发表时间：
2019-08-01
期刊：
影响因子：
17.1
通讯作者：
Ferreira, Lino
中科院分区：
文献类型：
--
作者：
Henriques-Antunes, Helena;Cardoso, Renato M. S.;Ferreira, Lino
小细胞外囊泡（SEV）为组织再生提供了一种有前途的策略，但它们在受损组织中的短暂寿命限制了它们的功效。在这里，我们表明 SEV 传递动力学在组织、细胞和分子水平上影响组织再生。我们表明，多次仔细定时应用 SEV 比单剂量相同总浓度的 SEV 具有更好的再生能力。重要的是，与使用单剂量或多剂量 SEV 或血小板衍生生长因子 BB（FDA 批准的伤口再生疗法）治疗的伤口相比，使用单时间点剂量的含有 SEV 的可注射光触发水凝胶治疗的糖尿病和非糖尿病伤口表现出闭合动力学的强劲增加。释放的 SEV 的促愈合活性在组织/细胞水平上通过皮肤新生血管形成和上皮再生的增加来介导，在分子水平上通过伤口愈合过程中不同时间 7 种 miRNA 表达的变化来介导。这包括 has-miR-150-5p 的改变，此处确定它对皮肤再生很重要。
Small extracellular vesicles (SEVs) offer a promising strategy for tissue regeneration, yet their short lifetime at the injured tissue limits their efficacy. Here, we show that kinetics of SEV delivery impacts tissue regeneration at tissue, cellular, and molecular levels. We show that multiple carefully timed applications of SEVs had superior regeneration than a single dose of the same total concentration of SEVs. Importantly, diabetic and non diabetic wounds treated with a single time point dose of an injectable light-triggerable hydrogel containing SEVs demonstrated a robust increase in closure kinetics relative to wounds treated with a single or multiple doses of SEVs or platelet-derived growth factor BB, an FDA-approved wound regenerative therapy. The pro-healing activity of released SEVs was mediated at the tissue/cell level by an increase in skin neovascularization and re-epithelization and at the molecular level by an alteration in the expression of 7 miRNAs at different times during wound healing. This includes an alteration of has-miR-150-5p, identified here to be important for skin regeneration.