title: Decellularized human liver as a natural 3D-scaffold for liver bioengineering and transplantation.
abstract: Liver synthetic and metabolic function can only be optimised by the growth of cells within a supportive liver matrix. This can be achieved by the utilisation of decellularised human liver tissue. Here we demonstrate complete decellularization of whole human liver and lobes to form an extracellular matrix scaffold with a preserved architecture. Decellularized human liver cubic scaffolds were repopulated for up to 21 days using human cell lines hepatic stellate cells (LX2), hepatocellular carcinoma (Sk-Hep-1) and hepatoblastoma (HepG2), with excellent viability, motility and proliferation and remodelling of the extracellular matrix. Biocompatibility was demonstrated by either omental or subcutaneous xenotransplantation of liver scaffold cubes (5 × 5 × 5 mm) into immune competent mice resulting in absent foreign body responses. We demonstrate decellularization of human liver and repopulation with derived human liver cells. This is a key advance in bioartificial liver development.
authors.affiliation: UCL, Institute for Liver and Digestive Health, University College London, London UK.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mazza
authors.affiliation: UCL, Institute for Liver and Digestive Health, University College London, London UK.
authors.forename: Krista
authors.initials: K
authors.lastname: Rombouts
authors.affiliation: UCL, Institute for Liver and Digestive Health, University College London, London UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Rennie Hall
authors.affiliation: Stem Cells and Regenerative Medicine Section, Developmental Biology and Cancer Programme, UCL Institute for Child Health, Great Ormond Street Hospital. University College London, London UK.
authors.forename: Luca
authors.initials: L
authors.lastname: Urbani
authors.affiliation: UCL, Institute for Liver and Digestive Health, University College London, London UK.
authors.forename: Tu
authors.initials: T
authors.lastname: Vinh Luong
authors.affiliation: UCL, Institute for Liver and Digestive Health, University College London, London UK.
authors.forename: Walid
authors.initials: W
authors.lastname: Al-Akkad
authors.affiliation: UCL, Institute for Liver and Digestive Health, University College London, London UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Longato
authors.affiliation: UCL, Institute for Liver and Digestive Health, University College London, London UK.
authors.forename: David
authors.initials: D
authors.lastname: Brown
authors.affiliation: Stem Cells and Regenerative Medicine Section, Developmental Biology and Cancer Programme, UCL Institute for Child Health, Great Ormond Street Hospital. University College London, London UK.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Maghsoudlou
authors.affiliation: Department of Cellular Pathology, UCL Medical School, Royal Free Campus, London UK.
authors.forename: Amar P
authors.initials: AP
authors.lastname: Dhillon
authors.affiliation: Division of Surgery, Royal Free London Foundation Trust. University College London, London UK.
authors.forename: Barry
authors.initials: B
authors.lastname: Fuller
authors.affiliation: Division of Surgery, Royal Free London Foundation Trust. University College London, London UK.
authors.forename: Brian
authors.initials: B
authors.lastname: Davidson
authors.affiliation: UCL, Institute for Liver and Digestive Health, University College London, London UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Moore
authors.affiliation: UCL, Institute for Liver and Digestive Health, University College London, London UK.
authors.forename: Dipok
authors.initials: D
authors.lastname: Dhar
authors.affiliation: Stem Cells and Regenerative Medicine Section, Developmental Biology and Cancer Programme, UCL Institute for Child Health, Great Ormond Street Hospital. University College London, London UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: De Coppi
authors.affiliation: Division of Surgery, Royal Free London Foundation Trust. University College London, London UK.
authors.forename: Massimo
authors.initials: M
authors.lastname: Malago
authors.affiliation: UCL, Institute for Liver and Digestive Health, University College London, London UK.
authors.forename: Massimo
authors.initials: M
authors.lastname: Pinzani
mesh_terms: D000818:Animals; D057005:Bioengineering / Q000379:methods*; D001698:Biomedical Engineering / Q000379:methods; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000502:physiology; D056945:Hep G2 Cells; D055166:Hepatic Stellate Cells / Q000166:cytology; D018197:Hepatoblastoma / Q000473:pathology; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D008099:Liver / Q000166:cytology*; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014183:Transplantation, Heterologous / Q000379:methods*