Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization

Mazza, Giuseppe and Al-Akkad, Walid and Telese, Andrea and Longato, Lisa and Urbani, Luca and Robinson, Benjamin and Hall, Andrew and Kong, Kenny and Frenguelli, Luca and Marrone, Giusi and Willacy, Oliver and Shaeri, Mohsen and Burns, Alan and Malago, Massimo and Gilbertson, Janet and Rendell, Nigel and Moore, Kevin and Hughes, David and Notingher, Ioan and Jell, Gavin and Del Rio Hernandez, Armando and De Coppi, Paolo and Rombouts, Krista and Pinzani, Massimo (2017) Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization. Scientific Reports, 7 . 5534/1-5534/14. ISSN 2045-2322

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Abstract

The development of human liver scaffolds retaining their 3-dimensional structure and extra-cellular matrix (ECM) composition is essential for the advancement of liver tissue engineering. We report the design and validation of a new methodology for the rapid and accurate production of human acellular liver tissue cubes (ALTCs) using normal liver tissue unsuitable for transplantation. The application of high shear stress is a key methodological determinant accelerating the process of tissue decellularization while maintaining ECM protein composition, 3D-architecture and physico-chemical properties of the native tissue. ALTCs were engineered with human parenchymal and non-parenchymal liver cell lines (HepG2 and LX2 cells, respectively), human umbilical vein endothelial cells (HUVEC), as well as primary human hepatocytes and hepatic stellate cells. Both parenchymal and non-parenchymal liver cells grown in ALTCs exhibited markedly different gene expression when compared to standard 2D cell cultures. Remarkably, HUVEC cells naturally migrated in the ECM scaffold and spontaneously repopulated the lining of decellularized vessels. The metabolic function and protein synthesis of engineered liver scaffolds with human primary hepatocytes reseeded under dynamic conditions were maintained. These results provide a solid basis for the establishment of effective protocols aimed at recreating human liver tissue in vitro.

Item Type: Article
Keywords: Biomaterials, Tissue engineering
Schools/Departments: University of Nottingham, UK > Faculty of Science > School of Physics and Astronomy
Identification Number: 10.1038/s41598-017-05134-1
Depositing User: Eprints, Support
Date Deposited: 10 Oct 2017 09:59
Last Modified: 14 Oct 2017 08:50
URI: http://eprints.nottingham.ac.uk/id/eprint/47111

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