Researchers generated cholangiocytes derived from human pluripotent stem cells (hPSCs) that displayed many characteristics of mature bile duct cells, as published in Nature Communications.
These cholangiocytes could be used to study the development and function of mature bile duct cells. They could also be used to develop new treatment options to restore bile duct function in patients with biliary diseases such as Alagille syndrome.
In Alagille syndrome, defects in the Notch signaling pathway lead to bile duct paucity, causing bile to build up in the liver which results in liver damage.
There is currently no cure for Alagille syndrome, and treatment options focus on increasing bile flow and supporting growth. There are also surgical care options such as biliary diversion and in more serious cases, liver transplantation.
A team of researchers led by Shinichiro Ogawa MD, PhD, described how they developed a monolayer-based differentiation strategy that yielded high numbers of mature cholangiocytes from hPSC lines.
Read more about Alagille syndrome etiology
They found 4 biological pathways: retinoic acid, BMP, cAMP, and Rho kinase inhibitors. These pathways play a key role in regulating the maturation of cholangiocytes.
The cells that were generated using this approach have characteristics that are essential for drug screening, the researchers said. They are also able to migrate to the liver when injected into the spleen of an immunocompromised mouse model and give rise to cells that possess the characteristics of mature cholangiocytes.
Therefore, these cells could not only help better study liver diseases such as Alagille syndrome, but they could also provide the basis to develop new therapies for them.
Cholnagiocytes are epithelial cells that form the bile ducts and have an essential function. They are responsible for regulating the viscosity and osmolality of the bile as it moves through the liver.
Ogawa M, Jiang JX, Xia S, et al. Generation of functional ciliated cholangiocytes from human pluripotent stem cells. Nat Commun. 2021;12(1):6504. doi:10.1038/s41467-021-26764-0