Boosting the Biogenesis and Secretion of Mesenchymal Stem Cell-Derived Exosomes
Boosting the Biogenesis and Secretion of Mesenchymal Stem Cell-Derived Exosomes
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促进间充质干细胞衍生的外泌体的生物发生和分泌
DOI：
10.3390/cells9030660
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发表时间：
2020-03-01
期刊：
影响因子：
6
通讯作者：
Nguyen, Juliane
中科院分区：
文献类型：
--
作者：
Wang, Jinli;Bonacquisti, Emily E.;Nguyen, Juliane
利用外泌体发挥其最大潜力的限制是它们从细胞中的有限分泌，这是有效外泌体生产和应用的主要瓶颈。这对于间充质干细胞（MSC）尤其如此，其可以自我更新但具有有限的扩增能力，仅在几次传代后经历衰老，与年轻细胞相比，源自衰老干细胞的外泌体显示出受损的再生能力。在这里，我们研究了能够增强MSC的外泌体分泌的小分子调节剂的作用。用N-甲基多巴胺和去甲肾上腺素的组合处理MSC使外来体产生稳健地增加了三倍，而不改变MSC外来体诱导血管生成、使巨噬细胞转化为抗炎表型或下调胶原蛋白表达的能力。这些小分子调节剂提供了一种有希望的方法来增加MSC的外泌体产生。
A limitation of using exosomes to their fullest potential is their limited secretion from cells, a major bottleneck to efficient exosome production and application. This is especially true for mesenchymal stem cells (MSCs), which can self-renew but have a limited expansion capacity, undergoing senescence after only a few passages, with exosomes derived from senescent stem cells showing impaired regenerative capacity compared to young cells. Here, we examined the effects of small molecule modulators capable of enhancing exosome secretion from MSCs. The treatment of MSCs with a combination of N-methyldopamine and norepinephrine robustly increased exosome production by three-fold without altering the ability of the MSC exosomes to induce angiogenesis, polarize macrophages to an anti-inflammatory phenotype, or downregulate collagen expression. These small molecule modulators provide a promising means to increase exosome production by MSCs.