Arificial biliary duct model for surgical therapeutic material and research material for biliary cancer

点击翻译按钮获取中文摘要

Artificial bile duct may be useful as surgical material and for studying the pathological and therapeutic mechanisms of biliary disease such as bile duct cancer. We reconstituted 3-dimensional artificial bile duct consisting biliary epithelial monolayer and connective tissue sub-layer. We first prepared a tubular structured tissue composed of human fibroblast and collagen gel using a tubular glass mold composed of a mandrel and a sheath. Then, a hybrid tissue with a hierarchical structure was constructed by seeding human biliary epithelial cells and the tubular tissue. The greatest size of the artificial bile duct that we have made before is 1 X 5 cm. The engineering of bile duct has been studied from a variety of approaches. (1) We examined if bile acid can injure the epithelium of the duct. The morphological injury effect of bile acid is less on biliary epithelium than in human mesothelial cells. (2) We transfected IFN-γ gene to the epithelium and fibroblast. However, IFN-γ secretion could not be observed. (3) We are now preparing bile duct cancer model exchanging the epithelium to human bile duct cancer cell line. (4) To apply the artificial duct for surgical implantation, we tested the mechanical strength. The duct tolerated luminal pressures well but not the mechanical stress applied during an anasotmotic procedure. To overcome the problem that artificial bile duct of collagen gel was torn easily during suturing of grafting, we prepare histocompatible collagen mesh and attached the mesh to the bottom of the connective tissue. One of the problems of preparing artificial bile duct is a difficulty in culturing a large number of biliary epithelial cells. We are now developing a new culture method using microgravity culture condition to obtain the 3-dimensional tissue seeded by a large number of biliary epithelial cells on connective tissue.