Decellularized human liver as a natural 3D-scaffold for liver bioengineering and transplantation

Giuseppe Mazza(University College London), Krista Rombouts(University College London), Andrew Hall(University College London), Luca Urbani(Great Ormond Street Hospital), Tu Vinh Luong(University College London), Walid Al‐Akkad(University College London), Lisa Longato(University College London), David Alan Brown(University College London), Panagiotis Maghsoudlou(Great Ormond Street Hospital), Amar P. Dhillon(The Royal Free Hospital), Barry Fuller(Royal Free London NHS Foundation Trust), Brian R Davidson(Royal Free London NHS Foundation Trust), Kevin Moore(University College London), Dipok Kumar Dhar(University College London), Paolo De Coppi(Great Ormond Street Hospital), Massimo Malagó(Royal Free London NHS Foundation Trust), Massimo Pinzani(University College London)
Scientific Reports
August 7, 2015
Cited by 408Open Access
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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.


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