间充质间质细胞胞外囊泡减少假单胞菌生物膜的形成,并使let-7b-5p负载具有额外的抗炎作用。

IF 3.5 2区 医学 Q1 PHYSIOLOGY
Sharanya Sarkar, Roxanna Barnaby, Amanda B Nymon, Lily A Charpentier, Lily Taub, Matthew J Wargo, Daniel J Weiss, Tracey L Bonfield, Bruce A Stanton
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引用次数: 0

摘要

囊性纤维化(CF)是一种由CFTR基因突变引起的多器官疾病,可导致慢性肺部感染和过度炎症。在CF肺部定植的病原体中,铜绿假单胞菌占主导地位,感染超过50%的CF成人,并随着时间的推移产生抗生素耐药性。目前CF的治疗方法,虽然提供了巨大的好处,但不能消除持续的细菌感染,慢性炎症和不可逆的肺损伤,需要新的治疗策略。我们的团队设计了间充质基质细胞衍生的细胞外囊泡(MSC EVs)来携带microRNA let-7b-5p作为抗感染和抗炎的双重治疗。MSC ev是具有天然抗菌和免疫调节特性的低免疫原性平台,而let-7b-5p可减轻炎症。本研究表明,MSC ev有效地阻断了原代人支气管上皮细胞(pHBECs)上耐抗生素铜绿假单胞菌生物膜的形成,并且通过减少pHBECs诱导的铜绿假单胞菌诱导的IL-8分泌,让-7b-5p加载到MSC ev中,具有额外的抗炎作用。这种方法有望改善CF患者的治疗效果,未来的工作将集中在优化给药策略和扩大MSC ev的临床适用性,以靶向其他CF相关病原体。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mesenchymal Stromal Cell Extracellular Vesicles Reduce Pseudomonas Biofilm Formation, and let-7b-5p Loading Confers Additional Anti-Inflammatory Effects.

Cystic Fibrosis (CF) is a multiorgan disease caused by mutations in the CFTR gene, leading to chronic pulmonary infections and hyperinflammation. Among pathogens colonizing the CF lung, Pseudomonas aeruginosa is predominant, infecting over 50% of adults with CF, and becoming antibiotic-resistant over time. Current therapies for CF, while providing tremendous benefits, fail to eliminate persistent bacterial infections, chronic inflammation, and irreversible lung damage, necessitating novel therapeutic strategies. Our group engineered mesenchymal stromal cell derived extracellular vesicles (MSC EVs) to carry the microRNA let-7b-5p as a dual anti-infective and anti-inflammatory treatment. MSC EVs are low-immunogenicity platforms with innate antimicrobial and immunomodulatory properties, while let-7b-5p reduces inflammation. This study demonstrates that MSC EVs effectively blocked the formation of antibiotic-resistant P. aeruginosa biofilms on primary Human Bronchial Epithelial Cells (pHBECs), and let-7b-5p loading into MSC EVs conferred additional anti-inflammatory effects by reducing P. aeruginosa-induced IL-8 secretion by pHBECs. This approach holds promise for improving outcomes for people with CF, and future work will focus on optimizing delivery strategies and expanding the clinical applicability of MSC EVs to target other CF-associated pathogens.

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来源期刊
CiteScore
9.20
自引率
4.10%
发文量
146
审稿时长
2 months
期刊介绍: The American Journal of Physiology-Lung Cellular and Molecular Physiology publishes original research covering the broad scope of molecular, cellular, and integrative aspects of normal and abnormal function of cells and components of the respiratory system. Areas of interest include conducting airways, pulmonary circulation, lung endothelial and epithelial cells, the pleura, neuroendocrine and immunologic cells in the lung, neural cells involved in control of breathing, and cells of the diaphragm and thoracic muscles. The processes to be covered in the Journal include gas-exchange, metabolic control at the cellular level, intracellular signaling, gene expression, genomics, macromolecules and their turnover, cell-cell and cell-matrix interactions, cell motility, secretory mechanisms, membrane function, surfactant, matrix components, mucus and lining materials, lung defenses, macrophage function, transport of salt, water and protein, development and differentiation of the respiratory system, and response to the environment.
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