Nebulised mesenchymal stem cell derived extracellular vesicles ameliorate E. coli induced pneumonia in a rodent model.
Nebulised mesenchymal stem cell derived extracellular vesicles ameliorate E. coli induced pneumonia in a rodent model.
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DOI：
10.1186/s13287-023-03385-6
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发表时间：
2023-06-06
影响因子：
7.5
通讯作者：
O'Toole, Daniel
中科院分区：
文献类型：
--
作者：
Gonzalez, Hector;McCarthy, Sean;Masterson, Claire;Byrnes, Declan;Sallent, Ignacio;Horan, Emma;Elliman, Stephen J.;Vella, Gabriele;Mello, Adriele P.;Silva, Johnatas D.;Krasnodembskaya, Anna D.;MacLoughlin, Ronan;Laffey, John G.;O'Toole, Daniel
关键词：
间充质干细胞（MSC）衍生的细胞外囊泡（EV）已被提出作为细胞治疗的替代方案，创造了新的可能的递送方式，如雾化。我们希望研究直接雾化MSC-EV在减轻大肠杆菌诱导的肺炎方面的治疗潜力。在雾化前和雾化后评估EV大小、表面标志物和miRNA含量。将BEAS 2B和A459肺细胞暴露于脂多糖（LPS），并用雾化的骨髓（BM）或脐带（UC）MSC-EV处理。进行活力测定（MTT）和炎性细胞因子测定。用LPS和雾化的BM-或UC-EV刺激THP-1单核细胞，并测量吞噬活性。对于体内实验，小鼠经气管内（IT）接受LPS，随后经静脉内（IV）接受BM-或UC-EV，并在24小时评估损伤标志物。大鼠灌胃E.大肠杆菌细菌IT和BM-或UC-EV IV或通过直接雾化递送。在48小时，通过生理参数、组织学和炎性标志物的存在来评估肺损伤。在体外雾化后，MSC-EV保留了其免疫调节和伤口愈合能力。EV的完整性和内容也得到了保留。静脉注射或雾化吸入MSC-EV治疗可降低LPS诱导的肺损伤的严重程度，E。通过减少细菌负荷和水肿，增加血氧和改善肺组织学评分来治疗大肠杆菌诱导的肺炎。MSC-EV治疗的动物也显示出较低水平的炎性细胞因子和炎性相关标志物。静脉注射MSC-EV可减轻LPS诱导的肺损伤，雾化吸入MSC-EV并不影响其减轻E.大肠杆菌肺炎，如细菌负荷减少和肺生理学改善所证明的。在线版本包含补充材料，可通过10.1186/s13287-023-03385-6获得。
Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) have been proposed as an alternative to cell therapy, creating new possible delivery modalities such as nebulisation. We wished to investigate the therapeutic potential of directly nebulised MSC-EVs in the mitigation of Escherichia coli-induced pneumonia. EV size, surface markers and miRNA content were assessed pre- and post-nebulisation. BEAS2B and A459 lung cells were exposed to lipopolysaccharide (LPS) and treated with nebulised bone marrow (BM) or umbilical cord (UC) MSC-EVs. Viability assays (MTT) and inflammatory cytokine assays were performed. THP-1 monocytes were stimulated with LPS and nebulised BM- or UC-EVs and phagocytosis activity was measured. For in vivo experiments, mice received LPS intratracheally (IT) followed by BM- or UC-EVs intravenously (IV) and injury markers assessed at 24 h. Rats were instilled with E. coli bacteria IT and BM- or UC-EVs delivered IV or by direct nebulisation. At 48 h, lung damage was assessed by physiological parameters, histology and inflammatory marker presence. MSC-EVs retained their immunomodulatory and wound healing capacity after nebulisation in vitro. EV integrity and content were also preserved. Therapy with IV or nebulised MSC-EVs reduced the severity of LPS-induced lung injury and E. coli-induced pneumonia by reducing bacterial load and oedema, increasing blood oxygenation and improving lung histological scores. MSC-EV treated animals also showed lower levels of inflammatory cytokines and inflammatory-related markers. MSC-EVs given IV attenuated LPS-induced lung injury, and nebulisation of MSC-EVs did not affect their capacity to attenuate lung injury caused by E. coli pneumonia, as evidenced by reduction in bacterial load and improved lung physiology. The online version contains supplementary material available at 10.1186/s13287-023-03385-6.
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影响因子：
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作者：
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