Laboratory of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Cardiology, Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Nanomedicine. 2019 Aug;20:102014. doi: 10.1016/j.nano.2019.102014. Epub 2019 May 30.
Exosomes are cell-derived extracellular vesicles of 30-150 nm in size and are involved in intercellular communication. Because of their bioactive cargo, consisting of proteins, RNA and lipids, and their natural ability to deliver these biomolecules to recipient cells, exosomes are increasingly being studied as novel drug delivery vehicles or as cell-free approaches to regenerative medicine. However, one of the major hurdles for clinical translation of therapeutic strategies based on exosomes is their low yield when produced under standard culture conditions. Exosomes are vesicles of endocytic origin and are released when multivesicular endosomes fuse with the plasma membrane. Here, we demonstrate that interfering with endolysosomal trafficking significantly increases exosome release. Furthermore, these exosomes retain their regenerative bioactivity as demonstrated by pro-survival and angiogenesis assays using both cardiomyocytes and endothelial cells. These results may be employed to increase exosome production for studying biological functions or to improve clinical translation of exosome-based therapeutics.
外泌体是直径为 30-150nm 的细胞来源的细胞外囊泡，参与细胞间通讯。由于其生物活性 cargo 包含蛋白质、RNA 和脂质，并且具有将这些生物分子递送到受体细胞的天然能力，因此外泌体越来越多地被研究作为新型药物递送载体或用于再生医学的无细胞方法。然而，基于外泌体的治疗策略的临床转化的主要障碍之一是它们在标准培养条件下产生时的产量低。外泌体是内体起源的囊泡，当多泡内体与质膜融合时释放。在这里，我们证明干扰内体运输可显著增加外泌体的释放。此外，这些外泌体保留了其再生生物活性，通过使用心肌细胞和内皮细胞的生存和血管生成测定来证明。这些结果可用于增加外泌体的产生，以研究生物学功能，或改善基于外泌体的治疗的临床转化。
