Neutrophil membrane engineered HucMSC sEVs alleviate cisplatin-induced AKI by enhancing cellular uptake and targeting.
Neutrophil membrane engineered HucMSC sEVs alleviate cisplatin-induced AKI by enhancing cellular uptake and targeting.
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中性粒细胞膜工程 HucMSC sEV 通过增强细胞摄取和靶向来减轻顺铂诱导的 AKI
DOI：
10.1186/s12951-022-01574-8
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发表时间：
2022-08-01
影响因子：
10.2
通讯作者：
Qian, Hui
中科院分区：
文献类型：
--
作者：
Wu, Peipei;Tang, Yuting;Jin, Can;Wang, Min;Li, Linli;Liu, Zhong;Shi, Hui;Sun, Zixuan;Hou, Xiaomei;Chen, Wenya;Xu, Wenrong;Qian, Hui
人脐带间充质干细胞衍生的小细胞外囊泡（hucMSC-sEV）已被证明是预防和治疗顺铂诱导的急性肾损伤（阿基）的治疗剂。然而，hucMSC-sEV在组织损伤的修复和治疗中仍然面临许多问题和挑战，包括循环时间短、靶向性不足和治疗效果低。因此，我们构建了与来自人中性粒细胞膜和hucMSC-sEV的纳米囊泡融合的工程化杂交囊泡，称为中性粒细胞膜工程化hucMSC-sEV（NEX）。NEX可显著增强hucMSC-sEVs对损伤肾组织的靶向性，通过降低促炎细胞因子表达改善受损肾功能，促进肾组织细胞增殖，抑制肾细胞凋亡。此外，NEX增强NRK 52 E细胞对hucMSC-sEV的摄取，但抑制RAW264.7细胞对hucMSC-sEV的摄取。此外，NEX的施用降低了细胞的氧化应激，并促进了体外顺铂处理的NRK 52 E细胞的增殖。总之，我们的研究结果表明，这种通用方法的设计增强了hucMSC-sEV在肾组织再生中的靶向和治疗效果，并为其临床应用提供了新的证据。在线版本包含补充材料，可通过10.1186/s12951-022-01574-8获得。
Human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (hucMSC-sEVs) have been demonstrated as a therapeutic agent to prevent and treat cisplatin-induced acute kidney injury (AKI). However, hucMSC-sEVs still face many problems and challenges in the repair and treatment of tissue injury, including short circulation time, insufficient targeting, and low therapeutic efficacy. Therefore, we constructed engineered hybrid vesicles fused with nanovesicles derived from human neutrophil membranes and hucMSC-sEVs, named neutrophil membrane engineered hucMSC-sEVs (NEX). NEX significantly enhanced the targeting of hucMSC-sEVs to injured kidney tissues, improved the impaired renal function via reducing pro-inflammatory cytokines expression, promoted the proliferation of renal tissue cells, and inhibited renal cell apoptosis in vivo. In addition, NEX enhanced hucMSC-sEVs uptake by NRK52E cells, but inhibited its uptake by RAW264.7 cells. Moreover, administration of NEX reduced cellular oxidative stress and promoted proliferation of NRK52E cells treated with cisplatin in vitro. In summary, our findings indicate that this design of a universal approach enhances the targeting and therapeutic efficacy of hucMSC-sEVs in kidney tissue regeneration, and provides new evidence promoting its clinical application. The online version contains supplementary material available at 10.1186/s12951-022-01574-8.
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