一个可扩展的人类肠-免疫共同培养模型,用于评估炎症性肠病的抗炎疗法
Swetha Peddibhotla1, Lauren A Boone1, Earnest L Taylor1
1Altis Biosystems, Inc. Durham, USA.
SLAS discovery : advancing life sciences R & D
|July 11, 2025
概括
使用肠道细胞和免疫细胞的新型共同培养模型有效模仿炎症性肠病 (IBD) 病理学. 该系统有助于选新的抗炎药物用于IBD治疗.
科学领域:
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
- 药物发现 药物发现 药物发现
背景情况:
- 目前的炎症性肠病 (IBD) 疗法面临着长期的无效性和患者不响应.
- 现有的动物和体外模型在准确反映IBD复杂的免疫-上皮相互作用方面存在局限性.
研究的目的:
- 开发一种复杂的体外模型,用于研究IBD中的免疫-上皮交叉.
- 创建一个与高通量查 (HTS) 兼容的系统,用于评估抗IBD疗法.
主要方法:
- 通过使用RepliGut® - 在TranswellTM系统上的平面横向结肠建立了初级肠上皮细胞共同培养系统.
- 将THP-1衍生的巨体纳入模型,以模拟先天性免疫信号和与肠道上皮的相互作用.
- 该模型使用脂聚糖 (LPS) 和干扰素- (IFN-γ) 进行了挑战,以模拟IBD类炎症.
主要成果:
- 与未刺激的巨细胞共同培养维持了上皮质屏障的完整性和细胞活力.
- 刺激的巨细胞损害了上皮完整性,降低了细胞活力,增加了炎症性细胞因子的释放,反映了IBD病理.
- 与阿达利穆马布和托法西提尼布的同时治疗成功地减轻了这些炎症影响.
结论:
- 开发的共同培养模型准确地复制了与IBD相关的关键炎症反应.
- 该系统展示了可复制性和可扩展性,使其适合用于抗炎药物的高通量查.
- 该模型提供了一个有前途的平台,可以加速新型IBD疗法的发现和转化.
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