Michalopoulos George K, Bowen William C, Mulè Karen, Lopez-Talavera Juan Carlos, Mars Wendy
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15102, USA.
Hepatology. 2002 Aug;36(2):278-83. doi: 10.1053/jhep.2002.34858.
Organoid cultures of hepatocytes in the presence of hepatocyte growth factor (HGF) and epidermal growth factor (EGF) display characteristic histologic organization. Biliary epithelium covers the surface of the tissue exposed to the culture medium. Hepatocytes, stellate cells and endothelial cells compose the underlying structures. In order to investigate the origin of the biliary epithelial cells in the organoid cultures, we utilized the retrorsine/DPPIV system of hepatocyte transplantation to create hybrid livers in which clones of DPPIV hepatocytes colonize variable portions of the lobules. We demonstrate that, as others have shown, biliary epithelium in this in vivo system remains that of the recipient (DPPIV negative) rat. Hepatocytes are the only cells positive for the DPPIV marker enzyme in the hybrid livers. Organoid cultures were prepared from the hybrid livers. Overall, 46.82% of the hepatocytes placed into culture were positive for DPPIV at time zero (after isolation). At 21 days in culture, 47.54% of the biliary epithelium on the surface of the organoid cultures was positive for DPPIV. Since the only DPPIV cells inoculated in the cultures were hepatocytes, this finding demonstrates that, in the conditions of the organoid cultures, hepatocytes do undergo phenotypic transition to biliary epithelial cells.
在肝细胞生长因子(HGF)和表皮生长因子(EGF)存在的情况下,肝细胞类器官培养物呈现出特征性的组织学结构。胆管上皮覆盖着暴露于培养基的组织表面。肝细胞、星状细胞和内皮细胞构成了其下的结构。为了研究类器官培养物中胆管上皮细胞的起源,我们利用了肝细胞移植的倒千里光碱/二肽基肽酶IV(DPPIV)系统来创建杂交肝脏,其中DPPIV肝细胞克隆定位于小叶的不同部分。我们证明,正如其他人所表明的,在这个体内系统中,胆管上皮仍然是受体(DPPIV阴性)大鼠的胆管上皮。肝细胞是杂交肝脏中唯一对DPPIV标记酶呈阳性的细胞。从杂交肝脏制备类器官培养物。总体而言,在培养开始时(分离后),接种到培养物中的肝细胞中有46.82%对DPPIV呈阳性。在培养21天时,类器官培养物表面47.54%的胆管上皮对DPPIV呈阳性。由于接种到培养物中的唯一DPPIV细胞是肝细胞,这一发现表明,在类器官培养条件下,肝细胞确实会发生向胆管上皮细胞的表型转变。