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

Mazza, Giuseppe; Al-Akkad, Walid; Telese, Andrea; Longato, Lisa; Urbani, Luca; Robinson, Benjamin; Hall, Andrew; Kong, Kenny; Frenguelli, Luca; Marrone, Giusi; Willacy, Oliver; Shaeri, Mohsen; Burns, Alan; Malago, Massimo; Gilbertson, Janet; Rendell, Nigel; Moore, Kevin; Hughes, David; Notingher, Ioan; Jell, Gavin; Del Rio Hernandez, Armando; De Coppi, Paolo; Rombouts, Krista; Pinzani, Massimo

Authors

Giuseppe Mazza

Walid Al-Akkad

Andrea Telese

Lisa Longato

Luca Urbani

Benjamin Robinson

Andrew Hall

Kenny Kong

Luca Frenguelli

Giusi Marrone

Oliver Willacy

Mohsen Shaeri

Alan Burns

Massimo Malago

Janet Gilbertson

Nigel Rendell

Kevin Moore

David Hughes

Ioan Notingher ioan.notingher@nottingham.ac.uk

Gavin Jell

Armando Del Rio Hernandez

Paolo De Coppi

Krista Rombouts

Massimo Pinzani



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.

Journal Article Type Article
Journal Scientific Reports
Print ISSN 2045-2322
Electronic ISSN 2045-2322
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 7
Article Number 5534
APA6 Citation Mazza, G., Al-Akkad, W., Telese, A., Longato, L., Urbani, L., Robinson, B., …Pinzani, M. (in press). Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization. Scientific Reports, 7, https://doi.org/10.1038/s41598-017-05134-1
DOI https://doi.org/10.1038/s41598-017-05134-1
Keywords Biomaterials, Tissue engineering
Publisher URL https://www.nature.com/articles/s41598-017-05134-1
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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