Exploring the use of precision-cut tissue slices to study biliary atresia
Exploring the use of precision-cut tissue slices to study biliary atresia
Biliary atresia (BA) is a rare disease of the bile ducts affecting neonates. Its pathophysiology remains largely unknown. This thesis of Jeske Fridrichs describes the development of two novel models for BA using precision-cut tissue slices (PCTS), a well-established method used to study organs.
Chapter 2 showed that it is possible to prepare and culture precision-cut cystic duct slices (PCCDS) and precision-cut gallbladder slices (PCGS) for at least 24 h. After incubation, we observed the formation of a new cell layer at the epithelium.
In chapter 3, we aimed to enhance epithelial regeneration using culture medium for cholangiocyte organoids. Our goal was to restore the epithelium via stimulation of the stem cell population. The use of this culture medium did not result in an increased epithelial regeneration or increased number of stem cells.
In chapter 4, we used the PCCDS model to study the toxin biliatresone. In our pilot study, we did not observe a toxic effect of biliatresone.
In chapter 5, we shifted our focus to the end-stage liver disease that can occur because of BA. We demonstrated that precision-cut biliary atresia liver slices (PCBALS) can be cultured up to 48 h and retain disease characteristics, which makes them a suitable platform for studying the mechanism of and treatments for BA-associated liver fibrosis.
Chapter 6 provided recommendations for optimization of the PCCDS and future use of the PCCDS and PCBALS. We hope that the findings of this thesis can contribute to future research into the pathophysiology of BA.