Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization
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...
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| Format: | Article |
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Nature Publishing Group
2017
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| Online Access: | https://eprints.nottingham.ac.uk/47111/ |
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| author | 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 |
| author_facet | 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 |
| author_sort | Mazza, Giuseppe |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T20:04:23Z |
| format | Article |
| id | nottingham-47111 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:04:23Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-471112020-05-04T18:55:40Z https://eprints.nottingham.ac.uk/47111/ 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 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. Nature Publishing Group 2017-07-17 Article PeerReviewed 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 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 Biomaterials Tissue engineering https://www.nature.com/articles/s41598-017-05134-1 doi:10.1038/s41598-017-05134-1 doi:10.1038/s41598-017-05134-1 |
| spellingShingle | Biomaterials Tissue engineering 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 Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization |
| title | 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_short | 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 |
| topic | Biomaterials Tissue engineering |
| url | https://eprints.nottingham.ac.uk/47111/ https://eprints.nottingham.ac.uk/47111/ https://eprints.nottingham.ac.uk/47111/ |