人类iPSC衍生的气道模型能够对健康和COPD支气管上皮的SARS-CoV-2感染进行比较分析
Lisa Morichon1,2, Jitendriya Swain1,3, Nathalie Gros1
1CEMIPAI: Centre d'Etudes des Maladies Infectieuses et Pharmacologie Anti-Infectieuses, CNRS UAR3725, 34293 Montpellier, France.
iScience
|March 5, 2026
概括
人类诱导的多能干细胞衍生呼吸道模型 (iALI) 显示,SARS-CoV-2在健康与COPD肺组织中引起持续感染和独特的免疫反应,影响治疗灵敏度.
科学领域:
- 呼吸系统医学 呼吸系统医学
- 病毒学 病毒学
- 干细胞生物学 干细胞生物学
背景情况:
- 严重急性呼吸道综合征-冠状病毒-2 (SARS-CoV-2) 导致显著的下呼吸道感染.
- 现有的人类模型缺乏完全复制长期SARS-CoV-2组织反应的能力.
研究的目的:
- 为了研究SARS-CoV-2感染动态和人类诱导的多能干细胞衍生的气道类似肠道 (iALI) 模型中的宿主反应.
- 为了比较健康和慢性阻塞性肺病 (COPD) 衍生的iALI模型之间的反应.
主要方法:
- 从健康和COPD捐赠者的hiPSC中生成iALI模型.
- 在iALI模型中感染SARS-CoV-2.
- 对病毒复制,细胞损伤 (损失),粘液产生和细胞因子分泌的分析.
- 评估免疫反应时间和抗病毒治疗敏感度.
主要成果:
- 在COPD中,SARS-CoV-2感染导致强大的病毒复制,持续性感染,乳毛损失,粘液增加和炎症增加.
- 与健康患者的延迟反应相比,COPD iALI显示出更早,更强的先天性免疫反应 (IL-2,CCL5,G-CSF,CXCL10的升高).
- 慢性肺炎iALI对抗病毒治疗的敏感性降低.
结论:
- iALI模型有效地重复了人类支气管组织中长期的SARS-CoV-2感染.
- 在支气管上皮质对SARS-CoV-2的反应中观察到捐赠者特定的差异,特别突出了COPD中过度炎症和改变的免疫时间.
- 这些iALI模型是研究呼吸道病毒感染和评估健康和患病肺部治疗策略的宝贵平台.
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