细胞外基质调节来自人类胚胎干细胞的肝细胞类细胞中的空间肝功能
Faiza Farhan1, Manjari Trivedi1, Priscilla Di Wu1
1Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.
Stem cell research & therapy
|November 1, 2023
概括
像Matrigel和原这样的细胞外基因组分对人类多能干细胞衍生的肝细胞样细胞 (HLCs) 产生差异性影响. 这些发现为产生用于药物开发和疾病建模的HLC提供了洞察力.
科学领域:
- 干细胞生物学 干细胞生物学
- 肝病学 肝病学是一种肝病学.
- 生物材料科学是生物材料的科学.
背景情况:
- 人类多能干细胞 (hPSC) 衍生的肝细胞样细胞 (HLC) 对疾病建模和药物开发至关重要.
- 从hPSCs中产生体内类似的HLC仍然是一个挑战.
- 细胞外矩阵 (ECM) 在hPSC肝脏分化中的作用尚未完全理解.
研究的目的:
- 调查Matrigel和I型原蛋白对hPSC肝脏分化的差异性影响.
- 在不同ECM上培养的HLCs的基因表达和功能.
- 评估ECM组件在模仿肝脏区分方面的潜力.
主要方法:
- 人类胚胎干细胞 (hESCs) 在二维和三维培养中使用多阶段协议分化为HLCs.
- 培养物在肝脏特异化和成熟过程中加入了I型原蛋白或Matrigel.
- 通过基因表达分析和功能测定 (例如,白蛋白,尿素,CYP3A4活性,糖原储存) 来表征HLC.
主要成果:
- 与Matrigel培养物相比,原培养的HLC显示了白蛋白和α-1抗素表达的增加和更高的尿素分泌.
- 马特里格尔培养的HLC表现出较高的CYP3A4活性和糖原储存.
- 原蛋白和Matrigel HLC之间的功能差异分别反映了周门肝细胞和周中心肝细胞.
结论:
- 凝和原对hPSC-HLC的分化和功能产生不同的影响.
- 这些ECM组件可以在体外部分重复肝脏区域化.
- 这些发现对于优化生物医学和临床应用hPSC-HLC生成具有重要意义.
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