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J. Funct. Biomater. 2015, 6(1), 16-32; doi:10.3390/jfb6010016

Poly(vinyl alcohol)/gelatin Hydrogels Cultured with HepG2 Cells as a 3D Model of Hepatocellular Carcinoma: A Morphological Study

1
Department of Clinical and Experimental Medicine, University of Pisa, via Savi 10, 56126 Pisa, Italy
2
Department of Surgical, Medical, Molecular Pathology and Emergency Medicine, University of Pisa, via Savi 10, 56126 Pisa, Italy
3
Laboratory of Creative Engineering & Design, the Biorobotics Institute, Scuola Superiore Sant'Anna, viale R. Piaggio 34, 56025 Pontedera (PI), Italy
*
Authors to whom correspondence should be addressed.
Academic Editor: Sue Anne Chew
Received: 17 November 2014 / Accepted: 5 January 2015 / Published: 13 January 2015
(This article belongs to the Special Issue Biomaterials Approaches for Cancer Research)
View Full-Text   |   Download PDF [5502 KB, uploaded 13 January 2015]   |  

Abstract

It has been demonstrated that three-dimensional (3D) cell culture models represent fundamental tools for the comprehension of cellular phenomena both for normal and cancerous tissues. Indeed, the microenvironment affects the cellular behavior as well as the response to drugs. In this study, we performed a morphological analysis on a hepatocarcinoma cell line, HepG2, grown for 24 days inside a bioartificial hydrogel composed of poly(vinyl alcohol) (PVA) and gelatin (G) to model a hepatocellular carcinoma (HCC) in 3D. Morphological features of PVA/G hydrogels were investigated, resulting to mimic the trabecular structure of liver parenchyma. A histologic analysis comparing the 3D models with HepG2 cell monolayers and tumor specimens was performed. In the 3D setting, HepG2 cells were viable and formed large cellular aggregates showing different morphotypes with zonal distribution. Furthermore, β-actin and α5β1 integrin revealed a morphotype-related expression; in particular, the frontline cells were characterized by a strong immunopositivity on a side border of their membrane, thus suggesting the formation of lamellipodia-like structures apt for migration. Based on these results, we propose PVA/G hydrogels as valuable substrates to develop a long term 3D HCC model that can be used to investigate important aspects of tumor biology related to migration phenomena. View Full-Text
Keywords: three-dimensional (3D); cancer model; poly(vinyl alcohol) (PVA); gelatin; HepG2; hepatocellular carcinoma (HCC); histology; cell morphology three-dimensional (3D); cancer model; poly(vinyl alcohol) (PVA); gelatin; HepG2; hepatocellular carcinoma (HCC); histology; cell morphology
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Moscato, S.; Ronca, F.; Campani, D.; Danti, S. Poly(vinyl alcohol)/gelatin Hydrogels Cultured with HepG2 Cells as a 3D Model of Hepatocellular Carcinoma: A Morphological Study. J. Funct. Biomater. 2015, 6, 16-32.

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