Branching cholangiocyte organoids from human cells
2022
University Medical Center Rotterdam, Rotterdam, Netherlands
Human cholangiocyte organoids show great promise for regenerative therapies and in vitro modelling of bile duct development and diseases. However, the cystic organoids lack the branching morphology of intrahepatic bile ducts (IHBDs). Here, the authors reported establishing human branching cholangiocyte organoid (BRCO) cultures. BRCOs self-organized into complex tubular structures resembling the IHBD architecture. Single-cell transcriptomics and functional analysis showed high similarity to primary cholangiocytes, and importantly, the branching growth mimicked aspects of tubular development and is dependent on JAG1/NOTCH2 signalling.
When applied to cholangiocarcinoma tumor organoids, the morphology changed to an in vitro morphology like primary tumors. Moreover, these branching cholangiocarcinoma organoids (BRCCAOs) better matched the transcriptomic profile of primary tumors and showed increased chemoresistance to gemcitabine and cisplatin. In conclusion, BRCOs recapitulate a complex process of branching morphogenesis in vitro. This provides an improved model to study the tubular formation, bile duct functionality, and associated biliary diseases.
Human branching cholangiocyte organoids recapitulate functional bile duct formation
Luc J.W. van der Laan
Added on: 02-06-2023
[1] https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00164-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1934590922001643%3Fshowall%3Dtrue#%20
