用于发育和疾病建模应用的hiPSC衍生肠道器官生成
Paulina M Durczak1, Kathryn L Fair1, Nicholas Jinks1
1Biodiscovery Institute, Translational Medical Sciences, School of Medicine, University of Nottingham.
Journal of visualized experiments : JoVE
|March 25, 2024
概括
人类诱导的多能干细胞衍生肠道器官被生成为模拟肠道发育和诸如炎症性肠病 (IBD) 这样的疾病. 这些有机体模仿人类肠道的结构和功能,为疾病建模和治疗目标发现提供了一个平台.
科学领域:
- 干细胞生物学 干细胞生物学
- 胃肠病学 胃肠病学
- 发育生物学是发展生物学.
背景情况:
- 人类诱导的多能干细胞 (hiPSCs) 可以分化成各种细胞类型.
- 肠道器官提供了一个用于研究人类肠道表皮的3D模型系统.
- 现有的模型可能无法完全回顾人类肠道疾病的复杂性.
研究的目的:
- 为了产生hiPSC衍生的肠道有机体.
- 为了对这些有机体进行成熟的肠道细胞类型和两极分化的特征.
- 建立研究人类肠道发育和疾病的模型,包括炎症性肠病 (IBD).
主要方法:
- 逐步分化hiPSCs成为最终的内皮,然后是后肠表皮.
- 用特定的生长因子和小分子 (SB202190,A83-01,Gastrin,Noggin,EGF,R-spondin-1,CHIR99021) 在细胞外基质 (ECM) 中进行3D培养.
- 使用qPCR和免疫细胞化学进行定期传递和表征.
主要成果:
- 成功生成了由hiPSC衍生的肠道有机体,具有密室/状结构.
- 已确认存在成熟的肠上皮细胞 (杯子,帕内斯,肠细胞) 和极分化 (维林表达).
- 器官对炎症介质 (TNF-α,TGF-β,LPS) 产生炎症和纤维化表型的反应.
结论:
- 来自hiPSC的肠道器官精确地模拟了人类肠道表皮及其发展.
- 这些有机体作为一个有价值的平台,用于模拟肠道疾病,如IBD.
- 这个模型系统可以帮助识别IBD的新型治疗点和生物标志物.
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