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.
Highlights
Recipient’s hepatocytes obtained from induced pluripotent stem cells and avoid the need for immunosuppression
The general liver tissue architecture appeared fully preserved as shown by Sirius Red staining for collagens (Fig. 2e) and Von Gieson staining for elastin (Fig. 2f)
The present paper describes our experience on the decellularization of human liver to generate human liver scaffolds
Summary
Recipient’s hepatocytes obtained from induced pluripotent stem (iPS) cells and avoid the need for immunosuppression. Liver cells could be obtained from human livers unsuitable for liver transplantation or following liver resection. In 2012, a further step onward was made with the repopulation of a pig liver scaffold with human foetal hepatocytes and stem cells[21]. The decellularization and repopulation of a human liver ECM scaffold with human derived liver cells has not been reported. To assess the capability of different types of human liver cells to repopulate hepatic ECM scaffolds (Fig. 1). The results of this study provide clear proof of concept data supporting the development of a bio-artificial liver tissue by employing decellularized human ECM liver scaffolds, opening, in general, more new possibilities in regenerative medicine for the use of donor human livers currently unsuitable for transplantation
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