Phenotypic regulation of liver cells in a biofunctionalized three-dimensional hydrogel platform

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...

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Bibliographic Details
Published in:Integrative biology (Cambridge) 2016-02, Vol.8 (2), p.156-166
Main Authors: Kim, Myung Hee, Kumar, Supriya K, Shirahama, Hitomi, Seo, Jeongeun, Lee, Jae Ho, Cho, Nam-Joon
Format: Article
Language:English
Subjects:
Acrylates - chemistry
Albumins - chemistry
Cell Adhesion
Cell Culture Techniques
Cell Line, Tumor
Cell Proliferation
Cell Survival
Collagen - chemistry
Colloids
Cytochrome P-450 Enzyme System - chemistry
Fibronectins - chemistry
Hepatocytes - cytology
Humans
Hydrogels - chemistry
Imaging, Three-Dimensional
Liver - cytology
Microspheres
Phenotype
Polyethylene Glycols - chemistry
Polystyrenes - chemistry
Porosity
Stress, Mechanical
Tissue Engineering - methods
Tissue Scaffolds
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Summary: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. Development of a biofunctionalized three-dimensional hydrogel scaffold for hepatoctye cell culture highlights the importance of cell morphology, more specifically sheet-layer formation, in regulating gene expression.
ISSN:1757-9694
1757-9708
DOI:10.1039/c5ib00269a