从多能干干细胞中衍生出具有功能性组织居民巨细胞的人类肠道器官,所有这些都是多能干细胞
Kentaro Tominaga1, Daniel O Kechele2, J Guillermo Sanchez2
1Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Center for Stem Cell and Organoid Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Cellular and molecular gastroenterology and hepatology
|December 19, 2024
概括
研究人员开发了一种具有功能性巨细胞的人体肠道有机体 (HIO) 模型. 这种先进的HIO系统可以模拟炎症性肠病,并研究肠道中的免疫细胞相互作用.
科学领域:
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
- 干细胞生物学 干细胞生物学
背景情况:
- 胃肠道器官是组织居民免疫细胞的宿主,对于发育,恒常性和疾病至关重要.
- 当前的人体器官模型,如人类肠道器官 (HIO),往往缺乏这些免疫细胞,限制了它们作为疾病模型的实用性.
- 在HIO中缺乏免疫细胞限制了它们作为研究疾病的准确化身的潜力.
研究的目的:
- 设计一种包含功能性组织居民巨体的人体肠道有机体 (HIO) 模型.
- 为研究胃肠道疾病创建一个更全面的器官系统.
主要方法:
- 人类多能干细胞分化产生HIO和巨细胞分别.
- 在2周内,HIO和巨细胞在体外共同培养.
- 通过转录概况,巨细胞功能测定或在免疫功能低下的小鼠体内成熟进行了10-12周的器官分析.
主要成果:
- 大细胞成功地集成到HIO中,在体外持续2周,体内持续至少12周.
- 同种植的巨体表现出类似于人类胎儿肠道巨体的转录特征,表明其获得了组织居民特征.
- HIO巨体表现出功能能力,包括细菌细胞酶和细胞因子的产生,以应对炎症刺激,通过介质蛋白-10调节.
结论:
- 一个具有功能性的,长期存在于组织中的巨细胞的新型HIO系统已经成功生成.
- 这种先进的有机体模型为研究炎症性肠病背后的复杂分子机制提供了宝贵的平台.
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