High frequency acoustic cell stimulation promotes exosome generation regulated by a calcium-dependent mechanism.
High frequency acoustic cell stimulation promotes exosome generation regulated by a calcium-dependent mechanism.
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DOI：
10.1038/s42003-020-01277-6
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发表时间：
2020-10-05
影响因子：
5.9
通讯作者：
Yeo LY
中科院分区：
文献类型：
--
作者：
Ambattu LA;Ramesan S;Dekiwadia C;Hanssen E;Li H;Yeo LY
外泌体是有前途的疾病诊断标志物和药物递送载体，尽管它们在实践中的使用受到可以产生的均匀量不足的限制。我们揭示，将细胞暴露于高频声辐射刺激它们的产生，而不损害细胞活力，通过利用它们的先天膜修复机制，其中钙离子从细胞外环境到细胞中的增强募集触发已知的协调外泌体产生的ESCRT途径。考虑到高的照射后细胞活力（> 95%），我们能够通过迭代照射和激发后孵育步骤再循环细胞，这促进了外泌体的同质群体的高通量生产，这是将外泌体疗法转化为临床实践的特别挑战。特别是，我们表明，在280分钟内仅用7个循环就可以实现产生的外泌体数量的约8至10倍富集，相当于约1.7-2.1倍/小时的产量。Ambattu等人报道了哺乳动物癌细胞的高频声刺激促进外泌体产生而不影响细胞活力。声刺激增加钙离子内流，其触发与外泌体产生相关的ESCRT途径。这种方法可以允许大规模的外泌体生产，具有潜在的临床应用。
Exosomes are promising disease diagnostic markers and drug delivery vehicles, although their use in practice is limited by insufficient homogeneous quantities that can be produced. We reveal that exposing cells to high frequency acoustic irradiation stimulates their generation without detriment to cell viability by exploiting their innate membrane repair mechanism, wherein the enhanced recruitment of calcium ions from the extracellular milieu into the cells triggers an ESCRT pathway known to orchestrate exosomal production. Given the high post-irradiation cell viabilities (≈95%), we are able to recycle the cells through iterative irradiation and post-excitation incubation steps, which facilitate high throughput production of a homogeneous population of exosomes—a particular challenge for translating exosome therapy into clinical practice. In particular, we show that approximately eight- to ten-fold enrichment in the number of exosomes produced can be achieved with just 7 cycles over 280 mins, equivalent to a yield of around 1.7–2.1-fold/h. Ambattu et al. report that high frequency acoustic stimulation of mammalian cancer cells promotes exosome generation without affecting cell viability. Acoustic stimulation increases calcium ion influx which triggers an ESCRT pathway related to exosome production. This method may allow for large-scale exosome production with potential clinical applications.
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