在实验性急性肺炎中,ARDS微环境通过VEGF增强MSC诱导的修复
Courteney Tunstead1, Evelina Volkova1, Hazel Dunbar1
1Cellular Immunology Lab, Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare, Ireland.
概括
在高炎症环境中预先授权介质细胞 (MSC) 增强它们对急性肺炎的疗效. 这种方法改善了小鼠的肺屏障完整性和临床结果,建议针对ARDS亚型量身定制的MSC治疗.
科学领域:
- 再生医学是一种再生医学.
- 免疫学 免疫学 免疫学
- 细胞疗法细胞疗法
背景情况:
- 介酶体 stromal 细胞 (MSCs) 在治疗急性呼吸困扰综合征 (ARDS) 等炎症性疾病方面表现出有限的疗效.
- ARDS呈现出明显的低-和超-炎症表型,可能会影响治疗反应.
- 细胞因子介导激活可以增强MSC的治疗潜力.
研究的目的:
- 调查是否在超炎症性ARDS环境中预许可MSC可以提高其在急性肺炎 (ALI) 中的治疗效果.
- 为了确定不同的ARDS炎症状态是否会对MSC功能产生不同的影响.
主要方法:
- 来自低和高炎症ARDS患者的血清 (基于IL-6水平) 用于许可MSCs.
- 用许可血清或健康的对照血清培养MSC.
- 在实验室和体内评估了MSC-CM对肺上皮细胞和ALI小鼠模型的影响.
主要成果:
- 超炎症性ARDS授权的MSC-CM (MSC-CMHyper) 通过血管内皮生长因子 (VEGF) 增强了紧结表达和肺上皮屏障完整性.
- 低和高炎症性ARDS授权的MSC-CM降低了ALI小鼠支气管支气管洗液中的IL-6和TNF-α水平.
- 只有MSC-CMHyper显著降低了ALI小鼠的肺透性,体重减轻和改善临床评分.
结论:
- ARDS的炎症环境通过差异调节MSC的细胞保护和免疫调节功能.
- 在高炎症环境中预先许可MSC可以提高其对ALI的治疗潜力.
- 根据ARDS表型量身定制MSC治疗可能会改善治疗结果.
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