Department of Respiratory Medicine, Clinical Research Center for Respiratory Disease, Xiangya Hospital, National Key Clinical Specialty, Branch of National, Central South University, No.28 Xiangya Road, Kai-Fu District, Changsha, 410008, Hunan, China.
Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
J Nanobiotechnology. 2023 Aug 25;21(1):295. doi: 10.1186/s12951-023-02038-3.
Acute lung injury (ALI), manifested as strong pulmonary inflammation and alveolar epithelial damage, is a life-threatening disease with high morbidity and mortality. Small extracellular vesicles (sEVs), secreted by multiple types of cells, are critical cellular communication mediators and can inhibit inflammation by transferring bioactive molecules, such as microRNAs (miRNAs). Thus, we hypothesized that sEVs derived from mesenchymal stromal cells (MSC sEVs) could transfer miRNAs to attenuate inflammation of lung epithelial cells during ALI.
C57BL/6 male mice were intratracheally administered LPS (10 mg/kg). Six hours later, the mice were randomly administered with MSC sEVs (40 µg per mouse in 150 µl of saline), which were collected by ultracentrifugation. Control group received saline administration. After 48 h, the mice were sacrificed to evaluate pulmonary microvascular permeability and inflammatory responses. In vitro, A549 cells and primary human small airway epithelial cells (SAECs) were stimulated with LPS with or without MSC sEVs treatment.
In vitro, MSC sEVs could also inhibit the inflammation induced by LPS in A549 cells and SAECs (reducing TNF-α, IL-1β, IL-6 and MCP-1). Moreover, MSC sEV treatment improved the survival rate, alleviated pulmonary microvascular permeability, and inhibited proinflammatory responses (reducing TNF-α, IL-1β, IL-6 and JE-1) in ALI mice. Notably, miR-223-3p was found to be served as a critical mediator in MSC sEV-induced regulatory effects through inhibition of poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1) in lung epithelial cells.
Overall, these findings suggest that MSC sEVs may offer a novel promising strategy for ALI.
急性肺损伤（ALI）表现为强烈的肺部炎症和肺泡上皮损伤，是一种发病率和死亡率都很高的危及生命的疾病。小细胞外囊泡（sEVs）由多种细胞分泌，是细胞间通讯的关键介质，可以通过转移如 microRNAs（miRNAs）等生物活性分子来抑制炎症。因此，我们假设间充质基质细胞（MSC sEVs）来源的 sEVs 可以将 miRNAs 转移到 ALI 期间的肺上皮细胞中，从而减轻炎症。
C57BL/6 雄性小鼠经气管内给予 LPS（10mg/kg）。6 小时后，随机给予 MSC sEVs（150μl 生理盐水 40μg 每只）。对照组给予生理盐水处理。48 小时后处死小鼠，评估肺微血管通透性和炎症反应。体外，用 LPS 刺激 A549 细胞和原代人小气道上皮细胞（SAECs），并用 MSC sEVs 处理。
体外，MSC sEVs 也可以抑制 LPS 诱导的 A549 细胞和 SAECs 的炎症（减少 TNF-α、IL-1β、IL-6 和 MCP-1）。此外，MSC sEV 处理可提高 ALI 小鼠的存活率，减轻肺微血管通透性，抑制促炎反应（减少 TNF-α、IL-1β、IL-6 和 JE-1）。值得注意的是，miR-223-3p 被发现是 MSC sEV 诱导的调节作用的关键介质，通过抑制肺上皮细胞中的多聚（腺苷二磷酸核糖）聚合酶-1（PARP-1）。
总的来说，这些发现表明 MSC sEVs 可能为 ALI 提供了一种新的有前途的策略。
