The treatment of common bile duct (CBD) disorders, such as biliary atresia or ischemic strictures, is restricted by the lack of biliary tissue from healthy donors suitable for surgical reconstruction. Here we report a new method for the isolation and propagation of human cholangiocytes from the extrahepatic biliary tree in the form of extrahepatic cholangiocyte organoids (ECOs) for regenerative medicine applications. The resulting ECOs closely resemble primary cholangiocytes in terms of their transcriptomic profile and functional properties. We explore the regenerative potential of these organoids in vivo and demonstrate that ECOs self-organize into bile duct-like tubes expressing biliary markers following transplantation under the kidney capsule of immunocompromised mice. In addition, when seeded on biodegradable scaffolds, ECOs form tissue-like structures retaining biliary characteristics. The resulting bioengineered tissue can reconstruct the gallbladder wall and repair the biliary epithelium following transplantation into a mouse model of injury. Furthermore, bioengineered artificial ducts can replace the native CBD, with no evidence of cholestasis or occlusion of the lumen. In conclusion, ECOs can successfully reconstruct the biliary tree, providing proof of principle for organ regeneration using human primary cholangiocytes expanded in vitro.

ObjectiveTo establish the accuracy of virtual hepatic resection using three-dimensional (3D) models constructed from computed tomography angioportography (CTAP) images in determining the liver volume (LV) resected during resectional liver surgery. Summary Background DataThe ability to measure LV before surgery could be useful in determining the extent and nature of hepatic resection. Accurate assessment of LV and an estimate of liver function may also allow prediction of postoperative liver failure in patients undergoing resection, assist in volume-enhancing embolization procedures, help with the planning of staged hepatic resection for bilobar disease, and aid in selection of living-related liver donors. MethodsA retrospective study was conducted involving 27 patients scheduled for liver resection. Using mapping technology, 3D models were constructed from helical CTAP images. From these 3D models, tumor volume, total LV, and functional LV were calculated and were compared with body weight. The 3D liver models were subjected to a virtual hepatectomy along established anatomical planes, and the resected LV was calculated. The resected volume predicted by radiologists (unaware of the actual weight) was compared with the specimen weight measured after actual surgical resection. ResultsA significant correlation was found between body weight and functional LV but not total LV. The computer prediction of resected LV after virtual hepatectomy of 3D models compared well with resected liver weight. ConclusionVirtual hepatectomy of 3D CTAP reconstructed images provides an accurate prediction of liver mass removed during subsequent hepatic resection. The authors intend to combine this technology with an assessment of liver function to attempt to predict patients at risk for liver failure after hepatic resection.

y Shared senior authorship.The objective was to determine whether metabolic goals have been achieved with locally isolated and transported preparations over the first 3 years of the UK's nationally funded integrated islet transplant program. Twenty islet recipients with C-peptide negative type 1 diabetes and recurrent severe hypoglycemia consented to the study, including standardized meal tolerance tests. Participants received a total of 35 infusions (seven recipients: single graft; 11 recipients: two grafts: two recipients: three grafts). Graft function was maintained in 80% at [median (interquartile range)] 24 (13.5-36) months postfirst transplant. Severe hypoglycemia was reduced from 20 (7-50) episodes/patient-year pretransplant to 0.3 (0-1.6) episodes/patient-year posttransplant (p < 0.001). Resolution of impaired hypoglycemia awareness was confirmed [pretransplant: Gold score 6 (5-7); 24 (13.5-36) months: 3 (1.5-4.5); p < 0.03]. Target HbA 1c of <7.0% was attained/maintained in 70% of recipients [pretransplant: 8.0 (7.0-9.6