Phenotypic regulation of liver cells in a biofunctionalized three-dimensional hydrogel platform
Phenotypic regulation of liver cells in a biofunctionalized three-dimensional hydrogel platform
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DOI：
10.1039/c5ib00269a
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发表时间：
2016-01-01
影响因子：
2.5
通讯作者：
Cho, Nam-Joon
中科院分区：
文献类型：
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作者：
Kim, Myung Hee;Kumar, Supriya K.;Cho, Nam-Joon
功能丧失是在二维（2D）细胞培养平台上培养的肝细胞面临的主要挑战。通过微制造策略产生的生物功能化三维（3D）支架可以通过呈现重要的环境线索、强大的机械性能和三维几何形状来克服这些限制，以实现高保真的肝脏组织工程。在此，我们报告了肝癌（Huh 7.5）细胞行为的胶原功能化微球模板聚（乙二醇）（PEG）水凝胶支架，促进三维肝片形态的详细调查。胶原结合导致改善肝脏特异性功能，包括白蛋白产生和细胞色素P450（CYP 450）活性。重要的是，许多细胞粘附标记物的基因表达随着刺激的先天肝细胞纤连蛋白的产生而沿着增强。总之，这些发现揭示了肝细胞形态和基因表达之间的密切联系，提供了证据表明3D水凝胶平台中的表面包被胶原蛋白触发了肝细胞特异性转录因子的上调和肝脏代谢标志物的分泌。
Loss of function is a major challenge for hepatocytes that are cultured on two-dimensional (2D) cell culture platforms. Biofunctionalized three-dimensional (3D) scaffolds produced by microfabrication strategies can overcome these limitations by presenting vital environmental cues, strong mechanical properties, and three-dimensional geometry to enable high-fidelity liver tissue engineering. Herein, we report the detailed investigation of hepatocarcinoma (Huh 7.5) cellular behavior in a collagen-functionalized microsphere-templated poly(ethylene glycol) (PEG) hydrogel scaffold which promotes 3D hepatic sheet morphology. Collagen conjugation led to improved liver-specific functions, including albumin production and cytochrome P450 (CYP450) activity. Importantly, the gene expression of numerous cell-adhesion markers was enhanced along with stimulated innate hepatocyte fibronectin production. Taken together, the findings reveal a close connection between hepatic cell morphology and gene expression, offering evidence that surface-coated collagen in the 3D hydrogel platform triggers the upregulation of hepatocyte-specific transcription factors and the secretion of liver metabolic markers.