Reproducible Large-Scale Isolation of Exosomes from Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells and Their Application in Acute Kidney Injury
Reproducible Large-Scale Isolation of Exosomes from Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells and Their Application in Acute Kidney Injury
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DOI：
10.3390/ijms21134774
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发表时间：
2020-07-01
影响因子：
5.6
通讯作者：
Yi, Yong Weon
中科院分区：
文献类型：
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作者：
Lee, Jun Ho;Ha, Dae Hyun;Yi, Yong Weon
急性肾损伤（AKI）是一种致命的医学事件，由突然的肾损伤或衰竭引起，导致患者在几小时或几天内死亡。先前的研究表明，来源于各种间充质干细胞/基质细胞的外泌体（MSC-外泌体）对包括AKI在内的多种肾脏疾病实验动物模型中的肾损伤具有积极作用。然而，外泌体的大规模生产不仅在大型动物的临床前研究中是一个挑战，而且对于成功的临床应用也是一个挑战。在这方面，切向流过滤（TFF）适用于符合良好生产规范（GMP）的高质量外泌体的大规模生产。到目前为止，还没有关于使用TFF的研究报道，而是几乎完全使用超离心分离来分离外泌体，用于临床前研究中的AKI治疗应用。在这里，我们证明了使用TFF可重复地大规模生产源自脂肪组织来源的MSC的外泌体（ASC-外泌体），以及ASC-外泌体在顺铂诱导的大鼠AKI的致死模型中的救生作用。我们的研究结果表明，大规模稳定生产ASC-外泌体而不丧失功能的可能性及其在危及生命的疾病中的成功应用。
Acute kidney injury (AKI) is a fatal medical episode caused by sudden kidney damage or failure, leading to the death of patients within a few hours or days. Previous studies demonstrated that exosomes derived from various mesenchymal stem/stromal cells (MSC-exosomes) have positive effects on renal injuries in multiple experimental animal models of kidney diseases including AKI. However, the mass production of exosomes is a challenge not only in preclinical studies with large animals but also for successful clinical applications. In this respect, tangential flow filtration (TFF) is suitable for good manufacturing practice (GMP)-compliant large-scale production of high-quality exosomes. Until now, no studies have been reported on the use of TFF, but rather ultracentrifugation has been almost exclusively used, to isolate exosomes for AKI therapeutic application in preclinical studies. Here, we demonstrated the reproducible large-scale production of exosomes derived from adipose tissue-derived MSC (ASC-exosomes) using TFF and the lifesaving effect of the ASC-exosomes in a lethal model of cisplatin-induced rat AKI. Our results suggest the possibility of large-scale stable production of ASC-exosomes without loss of function and their successful application in life-threatening diseases.