二维和三维ECM和生物力学线索对人ipsc来源的肝祖细胞分化的影响。

IF 9.6 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Ishita Jain, Brock Grenci, Hyeon Ryoo, Yang Yuan, Salman R Khetani, Gregory H Underhill
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引用次数: 0

摘要

人类肝脏组织从诱导多能干细胞分化为药物筛选和疾病建模提供了一个强大的平台。虽然3D类器官系统有效地概括了组织发育,但对微环境参数的系统研究仍然具有挑战性。在这里,利用二维细胞微阵列和三维聚乙二醇(PEG)为基础的微孔,开发了互补的方法来检查人类干细胞来源的肝母细胞分化。高通量微阵列平台能够系统评估60种不同的微环境条件,将15种ECM组合物与4种生长因子处理相结合。观察到肝细胞和胆管细胞标志物的位置依赖性表达,包括HNF4a、SOX9和CK19,其分化模式在ECM和生长因子条件下有很大差异。基于这些发现,选择特定的ECM组合-胶原蛋白1,纤维连接蛋白及其组合-整合到模块化的3D PEG水凝胶系统中。这个3D平台提供了对微组织几何形状和基质组成的独立控制,从而可以研究肝脏分化的空间组织。通过这种结合高通量筛选和定义的3D培养的综合方法,建立了一个框架来剖析人类肝脏发育的微环境调节。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effect of 2D and 3D ECM and Biomechanical Cues on Human iPSC-Derived Liver Progenitor Cell Differentiation.

The differentiation of human liver tissue from induced pluripotent stem cells presents a powerful platform for drug screening and disease modeling. While 3D organoid systems effectively recapitulate tissue development, systematic investigation of microenvironmental parameters remains challenging. Here, complementary approaches are developed utilizing 2D cellular microarrays and 3D polyethylene glycol(PEG)-based microwells to examine human stem cell-derived hepatoblast differentiation. High-throughput microarray platform enables systematic evaluation of 60 distinct microenvironmental conditions, combining 15 ECM compositions with 4 growth factor treatments. Position-dependent expression of hepatocytic and cholangiocytic markers is observed including HNF4a, SOX9, and CK19, with differentiation patterns varying substantially across ECM and growth factor conditions. Based on these findings, specific ECM combinations are selected - Collagen 1, Fibronectin, and their combination - for integration into a modular 3D PEG hydrogel system. This 3D platform provides independent control over microtissue geometry and matrix composition, enabling investigation of spatial organization in hepatic differentiation. Through this integrated approach combining high-throughput screening and defined 3D culture, a framework is established for dissecting the microenvironmental regulation of human liver development.

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来源期刊
Advanced Healthcare Materials
Advanced Healthcare Materials 工程技术-生物材料
CiteScore
14.40
自引率
3.00%
发文量
600
审稿时长
1.8 months
期刊介绍: Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.
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