Liver transplantation is the only effective treatment for end-stage liver disease, but absolute donor shortage remains a limiting factor. Recent advances in tissue engineering focus on generation of native extracellular matrix (ECM) by decellularized complete livers in animal models. Although proof of concept has been reported for human livers, this study aims to perform whole liver decellularization in a clinically relevant series using controlled machine perfusion. In this study, we describe a mild nondestructive decellularization protocol, effective in 11 discarded human whole liver grafts to generate constructs that reliably maintain hepatic architecture and ECM components using machine perfusion, while completely removing cellular DNA and RNA. The decellularization process preserved the ultrastructural ECM components confirmed by histology, electron microscopy, and proteomic analysis. Anatomical characteristics of the native microvascular network and biliary drainage of the liver were confirmed by contrast computed tomography scanning. Decellularized vascular matrix remained suitable for normal suturing and no major histocompatibility complex molecules were detected, suggesting absence of allo-reactivity when used for transplantation. After extensive washing, decellularized scaffolds were nontoxic for cells after reseeding human mesenchymal stromal or umbilical vein endothelial endothelium cells. Indeed, evidence of effective recellularization of the vascular lining was obtained. In conclusion, we established an effective method to generate clinically applicable liver scaffolds from human discarded whole liver grafts and show proof of concept that reseeding of normal human cells in the scaffold is feasible. This supports new opportunities for bioengineering of transplantable grafts in the future.
Purpose: To explore the potential use of magnetic resonance imaging (MRI) in predicting the outcome for patients with hepatocellular carcinoma (HCC), imaging characteristics were correlated with pathological findings and clinical outcome.
Materials and Methods:With permission from the Ethical Board, clinical data and tissues of resected HCC patients were collected, including the preoperative MRI. The role of MRI characteristics on recurrence and survival were evaluated with univariate and multivariate analyses.Results: Between January 2000 and December 2008, 87 patients with 104 HCCs were operated on. Microvascular invasion was present in 55 lesions (53%). HCC was characterized as well differentiated in 15 lesions (14%), as moderate in 50 lesions (48%), and as poorly differentiated in 34 lesions (33%). Due to preoperative treatment in five lesions (5%) no vital tumor was left. In 85 lesions (88%) washout of contrast was noted. Of the 87 patients, 28 (32%) with 37 lesions developed HCC recurrence; these patients had microvascular invasion significantly more often and a moderate or poorly differentiated tumor (P < 0.001 and P ¼ 0.025, respectively). MRI more often showed washout when HCC was moderately or poorly differentiated (P < 0.001) or microvascular invasion was present (P ¼ 0.032).Conclusion: Differentiation grade and microvascular invasion are significantly associated with the presence of washout demonstrated on dynamic contrast-enhanced MRI.
In contrast to noninflammatory HCAs, inflammatory HCAs can show areas of iso- to hyperintensity to the surrounding liver in the hepatocyte phase; therefore, other typical imaging features should also be used to distinguish between HCAs and FNHs.
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