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

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...

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Autores principales:	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, Gavin Jell, Armando Del Rio Hernandez, Paolo De Coppi, Krista Rombouts, Massimo Pinzani
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/32ff58339b1d4b9d8761dceb964446e2
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spelling	oai:doaj.org-article:32ff58339b1d4b9d8761dceb964446e22021-12-02T15:04:52ZRapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization10.1038/s41598-017-05134-12045-2322https://doaj.org/article/32ff58339b1d4b9d8761dceb964446e22017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05134-1https://doaj.org/toc/2045-2322Abstract 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.Giuseppe MazzaWalid Al-AkkadAndrea TeleseLisa LongatoLuca UrbaniBenjamin RobinsonAndrew HallKenny KongLuca FrenguelliGiusi MarroneOliver WillacyMohsen ShaeriAlan BurnsMassimo MalagoJanet GilbertsonNigel RendellKevin MooreDavid HughesIoan NotingherGavin JellArmando Del Rio HernandezPaolo De CoppiKrista RomboutsMassimo PinzaniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Gavin Jell Armando Del Rio Hernandez Paolo De Coppi Krista Rombouts Massimo Pinzani Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization
description	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.
format	article
author	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 Gavin Jell Armando Del Rio Hernandez Paolo De Coppi Krista Rombouts Massimo Pinzani
author_facet	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 Gavin Jell Armando Del Rio Hernandez Paolo De Coppi Krista Rombouts Massimo Pinzani
author_sort	Giuseppe Mazza
title	Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization
title_short	Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization
title_full	Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization
title_fullStr	Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization
title_full_unstemmed	Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization
title_sort	rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/32ff58339b1d4b9d8761dceb964446e2
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Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization

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