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Sci Rep. 2017 Jul 17;7(1):5534. doi: 10.1038/s41598-017-05134-1.

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

Author information

1
UCL Institute for Liver and Digestive Health, Royal Free Hospital. University College London, London, UK. giuseppe.mazza.12@ucl.ac.uk.
2
UCL Institute for Liver and Digestive Health, Royal Free Hospital. University College London, London, UK.
3
Stem Cells and Regenerative Medicine Section, Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute for Child Health. University College London, London, UK.
4
Department of Bioengineering, Cellular and Molecular Biomechanics. Imperial College, London, UK.
5
School of Physics and Astronomy, University of Nottingham, Nottingham, UK.
6
CN Bio Innovations Limited. BioPark Hertfordshire, Broadwater Road, Welwyn Garden City, Hertfordshire, UK.
7
Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, Netherlands.
8
Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, Royal Free Hospital. University College London, London, UK.
9
Center for Nanotechnology and Regenerative Medicine, Division of Surgery and Interventional Science. University College London, London, UK.

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.

PMID:
28717194
PMCID:
PMC5514140
DOI:
10.1038/s41598-017-05134-1
[Indexed for MEDLINE]
Free PMC Article

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