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工程微组织模拟动态异型细胞信号传递对iPSC衍生的人类肝细胞成熟的影响

Regeant Panday¹, Kerry M Rogy¹, Yong Duk Han¹

¹Department of Biomedical Engineering, University of Illinois Chicago, 851 S Morgan St, 218 SEO, Chicago, IL 60607, USA.

Acta biomaterialia

|March 15, 2025

概括

开发功能人类肝脏模型对于药物查和疾病研究至关重要. 这项研究使用3D微组织与干细胞衍生的肝细胞和非体细胞,揭示特定的细胞组合增强肝细胞成熟,以获得更好的应用.

科学领域:

生物技术和再生医学生物技术和再生医学
干细胞生物学干细胞生物学
肝病学和药物新陈代谢

背景情况:

诱导多能干细胞衍生的肝细胞样细胞 (iHeps) 对体外肝脏模型至关重要,但往往缺乏功能成熟度.
在发育过程中,iHeps的成熟受到与非辅酶细胞 (NPC) 的相互作用的影响.
在体外复制这些动态细胞相互作用是理解和改善iHep成熟的关键.

研究的目的:

在3D微组织格式中,研究不同类型的非共生细胞 (NPC) 对诱导多能干细胞衍生的肝细胞样细胞 (iHeps) 的成熟的影响.
阐明NPC动态时空信号传递在促进iHep功能成熟中的作用.
为了确定特定的NPC和信号通路,增强iHep成熟,以改善体外肝脏模型.

主要方法:

高通量滴滴微流体被用于将iHeps封装在原I微凝中,形成3D微组织.
微组织与各种NPC类型 (例如胚胎纤维细胞,肝脏侧侧内皮细胞) 在微中共同培养.
动态的共同培养策略涉及不同NPC的顺序添加被用来建模发育信号.

主要成果:

与胚胎纤维细胞和肝脏阴侧内皮细胞 (LSECs) 共同培养显著提高了iHep成熟度,相比其他NPC类型.
一种顺序信号方法,引入胚胎纤维细胞刺激,然后进行LSEC刺激,产生了最高的iHep成熟度.
对LSEC/iHep微组织的基因表达分析揭示了类似成人原发性人肝细胞 (PHHs) 的成熟特征.

结论:

3D微组织为剖析调节iHep成熟的微环境线索提供了一个强大的平台.
特定的组合和NPC相互作用的动态序列对于实现成熟的iHep表型至关重要.
这种方法促进了用于药物发现和疾病研究的更生理相关的体外肝脏模型的开发.

关键词:

滴滴微流体学滴滴微流体学胚胎纤维细胞胚胎纤维细胞.肝脏肝脏肝脏肝脏肝脏的鼻状内皮细胞是肝脏内皮细胞.非基细胞的细胞.干细胞是一种干细胞.从iPSC衍生的肝细胞.

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