No abstract

Background: Cholangiopathies are increasingly recurrent and popular in people with liver diseases. Liver transplantation is undoubtedly the main treatment for these pathologies. Artificial bile duct has been regarded as an alternative and several reports have been published. However, a recurring phenomenon after surgery is the appearance of biliary stones, particularly pigment stones. For this reason, we try to reduce the incidence of biliary stone formation after replacement of artificial bile duct. We test several drugs and select ursodeoxycholic acid (UDCA) to prevent or minimize the generation of stones in the artificial bile duct. Methods: Human gallbladder stones were tested with different drugs including UDCA to evaluate their dissolution power. Pigment, cholesterol and mixed stones were treated with several drugs for several days to check their size reduction. Poly vinyl ethanol nanofibers were covered with UDCA for its gradual release into an aqueous medium. The human chemically derived hepatic progenitor cells (hCdHs) were differentiated into cholangiocytes (hCdH-Chols) and seeded on the nanofibers. Results: Compared to other drugs, UDCA showed the highest levels of dissolution at 120 h, which was reflected by the size of the stones. After this, the same procedure was carried out with cholesterol and mixed stones. UDCA showed similar effects, however its efficiency was lower and over a longer period of time. The hCdHs were seeded on UDCA-coated nanofibers and differentiated into cholangiocytes, the presence of UDCA favored differentiation of hCdHs to cholangiocytes. Conclusions: As a preliminary study, UDCA showed the most effective dissolution of gallbladder stones, especially in the pigment stones. Furthermor, UDCA-coated nanofiber benefits cholangiocellular differentiation from hCdHs in vitro. These findins indicated UDCA is one of the most available drugs which can be used for the generation of drug eluting artificial bile duct.

Background:The growing need for in vitro models that recapitulate the pathophysiological processes of liver diseases has led us to develop different approaches such as organoids which proved to be a suitable model for disease modeling, drug screening and regenerative medicine. Methods: Human chemically derived hepatic progenitor cells (hCdHs) were generated from hPHs cultured with reprogramming medium (HGF, A83-01 and CHIR99021) for 7 days. We generated organoids using hCdHs and liver cells cultured on Matrigel with organoid medium to obtain hCdHs derived liver organoids (hCdHOs) and human liver organoids (hLOs). Results: hCdHO and hLOs showed morphological but not genetic similarities, with hCdHOs having a more stemness profile. After treatment with hepatic differentiation medium (DM), hCdHO_DM showed clear hepatic characteristics. hCdHO_DM showed a higher sensitivity to drug treatment even than primary hepatocytes. Finally, under alcohol treatment these organoids showed the typical responses of alcoholic liver disease. Conclusions: Our hCdHOs present excellent features to position themselves as a novel model for disease modeling and toxicological analysis.