Use of decellularized porcine liver for engineering humanized liver organ.

BACKGROUND: New bioartificial liver devices are needed to supplement the limited supply of organ donors available for patients with end-stage liver disease. Here, we report the results of a pilot study aimed at developing a humanized porcine liver by transplanting second trimester human fetal hepatocytes (Hfh) co-cultured with fetal stellate cells (Hfsc) into the decellularized matrix of a porcine liver. MATERIAL AND METHODS: Ischemic livers were removed from 19 Yorkshire swine. Liver decellularization was achieved by an anionic detergent (SDS). The decellularized matrix of three separate porcine liver matrices was seeded with 3.5 × 10(8) and 1 × 10(9) of Hfsc and Hfh, respectively, and perfused for 3, 7, and 13 d. The metabolic and synthetic activities of the engrafted cells were assessed during and after perfusion. RESULTS: Immunohistologic examination of the decellularized matrix showed removal of nuclear materials with intact architecture and preserved extracellular matrix (ECM) proteins. During perfusion of the recellularized matrices, measurement of metabolic parameters (i.e., oxygen concentration, glucose consumption, and lactate and urea production) indicated active metabolism. The average human albumin concentration was 29.48 ± 7.4 µg/mL. Immunohistochemical analysis revealed cell differentiation into mature hepatocytes. Moreover, 40% of the engrafted cells were actively proliferating, and less than 30% of cells were apoptotic. CONCLUSION: We showed that our decellularization protocol successfully removed the cellular components of porcine livers while preserving the native architecture and most ECM protein. We also demonstrated the ability of the decellularized matrix to support and induce phenotypic maturation of engrafted Hfh in a continuously perfused system.

Biliary adenofibroma with carcinoma in situ: a rare case report.

This case report exhibits a rare biliary tumor within the liver of a 53-year-old Caucasian woman. This exophytic, multicystic, 6.5 × 5.0 cm mass was composed of complex tubulocystic structures lined by nonmucin-secreting, biliary epithelium embedded in fibrous stroma, consistent with biliary adenofibroma. This is the seventh case described in the literature. Multiple foci of high-grade dysplasia/carcinoma in situ were found with a microscopic focus of invasive carcinoma in review of the pathology, making this only the second case reporting malignant transformation. It is presented to illustrate the premalignant potential in a biliary epithelial tumor currently categorized as benign.