Researchers reported the development of organoid cultures initiated from bile samples obtained during routine clinical procedures and showed that these organoids are able to repopulate human extrahepatic bile duct scaffolds, as published in Clinical and Translational Medicine.
Alagille syndrome is a disease characterized by intrahepatic bile duct paucity. In the present study, a team of researchers led by Luc J. W. van der Laan, PhD, characterized bile cholangiocyte organoids and mirrored them to the already established organoids initiated cholangiocyte-like cells from intrahepatic and extrahepatic bile duct tissue biopsies.
Typically, invasive tissue biopsies that are associated with complications are necessary for organoid initiations. “We demonstrate successful organoid-initiation from extrahepatic bile collected from gallbladder after resection,” the researchers wrote. They reported that the organoids showed features similar to in vivo cholangiocytes.
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For example, bile cholangiocyte organoids derived from bile obtained via endoscopic retrograde pancreaticography exclusively expressed the bile duct genes HOXB2 and HOXB3. Similarly, gallbladder-derived organoids expressed gallbladder-specific genes.
The researchers also demonstrated that bile cholangiocyte organoids repopulated decellularized extrahepatic bile duct scaffolds effectively and restored the monolayer of cholangiocyte-like cells in vitro.
“Bile samples obtained through minimally invasive procedures provide a safe and effective alternative source of cholangiocyte organoids,” the authors said. “This opens new doors to study extrahepatic biliary diseases and regenerative medicine of the extrahepatic bile duct without the need of invasively collected biopsies.”
Organoids described in this study may not directly be useful for the development of potential new therapies for Alagille syndrome, however, could be used for bile duct tissue engineering and for personalized modeling of extrahepatic biliary diseases, they concluded.
Roos FJM, Wu H, Willemse J, et al. Cholangiocyte organoids from human bile retain a local phenotype and can repopulate bile ducts in vitro. Clin Transl Med. 2021;11(12):e566. doi:10.1002/ctm2.566