Li Zongying, Cao Shuyi
Department of Nephrology, Cangzhou Central Hospital, Cangzhou, Hebei Province, China.
Aging (Albany NY). 2020 Sep 23;12(18):18008-18018. doi: 10.18632/aging.103545.
The administration of cisplatin is limited due to its nephrotoxicity, and prevention of this nephrotoxicity of cisplatin is difficult. Mesenchymal stem cell (MSC)-derived exosomes have been implicated as a novel therapeutic approach for tissue injury.
In vitro, the NRK cells pre-incubated with HUMSC-exosomes increased the Cp-inhibited cell viability, proliferation activity, and the cell proportion in G1-phase and inhibited Cp-induced cell apoptosis. Furthermore, the expression levels of apoptotic marker proteins Bim, Bad, Bax, cleaved caspase-3, and cleaved caspase-9 induced by Cp in the NRK cells were decreased by pre-incubating with HUMSC-exosomes.
Our findings indicated that the exosomes from HUMSCs can effectively increase the survival rate and inhibit cell apoptosis of NRK cells. Therefore, pre-treatment of HUMSC-exosomes may be a new method to improve the therapeutic effect of cisplatin.
Exosomes were isolated from human umbilical cord derived mesenchymal stem cells (HUMSCs). Co-culture of normal rat renal tubular epithelial cells (NRK) and the absorption of exogenous exosomes by NRK cells were examined in vitro. Then the NRK cells were incubated with exosomes from HUMSCs and cisplatin (Cp). Cells were harvested for MTT assay, cloning formation, flow cytometry, and Western blot.
顺铂因其肾毒性而限制了其应用，且预防顺铂的这种肾毒性较为困难。间充质干细胞（MSC）来源的外泌体已被认为是一种治疗组织损伤的新方法。
在体外，用HUMSC-外泌体预孵育的NRK细胞提高了被顺铂抑制的细胞活力、增殖活性以及G1期的细胞比例，并抑制了顺铂诱导的细胞凋亡。此外，通过用HUMSC-外泌体预孵育，可降低顺铂在NRK细胞中诱导的凋亡标志物蛋白Bim、Bad、Bax、裂解的caspase-3和裂解的caspase-9的表达水平。
我们的研究结果表明，HUMSCs来源的外泌体可有效提高NRK细胞的存活率并抑制其细胞凋亡。因此，HUMSC-外泌体预处理可能是提高顺铂治疗效果的一种新方法。
从人脐带间充质干细胞（HUMSCs）中分离外泌体。体外检测正常大鼠肾小管上皮细胞（NRK）的共培养以及NRK细胞对外源外泌体的吸收。然后将NRK细胞与HUMSCs来源的外泌体和顺铂（Cp）一起孵育。收获细胞用于MTT法、克隆形成、流式细胞术和蛋白质免疫印迹分析。
