Extracellular vesicles (EVs) from cultured cells or bodily fluids have been demonstrated to show therapeutic value following myocardial infarction. However, challenges in donor variation, EV generation and isolation methods, and material availability have hindered their therapeutic use. Here, we show that human clinical-grade platelet concentrates from a blood establishment can be used to rapidly generate high concentrations of high purity EVs from sero-converted platelet lysate (SCPL-EVs) with minimal processing, using size-exclusion chromatography. Processing removed serum carrier proteins, coagulation factors and complement proteins from the original platelet lysate and the resultant SCPL-EVs carried a range of trophic factors and multiple recognised cardioprotective miRNAs. As such, SCPL-EVs protected rodent and human cardiomyocytes from hypoxia/re-oxygenation injury and stimulated angiogenesis of human cardiac microvessel endothelial cells. In a mouse model of myocardial infarction with reperfusion, SCPL-EV delivery using echo-guided intracavitary percutaneous injection produced large improvements in cardiac function, reduced scar formation and promoted angiogenesis. Since platelet-based biomaterials are already widely used clinically, we believe that this therapy could be rapidly suitable for a human clinical trial.

中文翻译：

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从血清转化的人血小板裂解物中纯化的细胞外囊泡在心脏缺血/再灌注损伤后提供强有力的保护

来自培养细胞或体液的细胞外囊泡（EV）已被证明在心肌梗塞后显示出治疗价值。然而，供体变异、EV产生和分离方法以及材料可用性方面的挑战阻碍了它们的治疗用途。在这里，我们表明，来自血液机构的人类临床级血小板浓缩物可用于使用尺寸排阻色谱法，通过最少的处理，从血清转化的血小板裂解物 (SCPL-EV) 快速产生高浓度的高纯度 EV。处理从原始血小板裂解物中去除了血清载体蛋白、凝血因子和补体蛋白，所得的 SCPL-EV 携带一系列营养因子和多种公认的心脏保护 miRNA。因此，SCPL-EV 可以保护啮齿动物和人类心肌细胞免受缺氧/再氧合损伤，并刺激人类心脏微血管内皮细胞的血管生成。在再灌注心肌梗死小鼠模型中，使用回波引导腔内经皮注射进行 SCPL-EV 递送可显着改善心脏功能，减少疤痕形成并促进血管生成。由于基于血小板的生物材料已经在临床上广泛使用，我们相信这种疗法可以迅速适用于人体临床试验。