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

脱细胞人肝作为肝脏生物工程和移植的天然三维支架

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作者:Giuseppe Mazza, Krista Rombouts, Andrew Rennie Hall, Luca Urbani, Tu Vinh Luong, Walid Al-Akkad, Lisa Longato, David Brown, Panagiotis Maghsoudlou, Amar P Dhillon, Barry Fuller, Brian Davidson, Kevin Moore, Dipok Dhar, Paolo De Coppi, Massimo Malago, Massimo Pinzani

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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