Year: 2012
Type: dissertation
Abstract: The identification of resident stem cells in the gallbladder and liver has great importance for basic biology and cell-based therapy. However, there is a paucity of data regarding gallbladder stem cells, especially in humans. In addition, the isolation of liver stem cells has been controversial in particular their ability to robustly generate hepatocytes that can engraft in vivo. The differences between gallbladder cells that are part of the extrahepatic bile duct system and intrahepatic bile duct cells have not yet been explored. Finally, the identification of gallbladder stem cells could represent an alternative source of hepatocytes for cell-based therapy to cure end stage liver disease. This is because gallbladder and liver cells are developmentally related and the removal of adult human gallbladders is relatively common surgery, thereby providing a large source of donor tissue. In this study, we focus on developing in vitro expansion and differentiation assays to evaluate bile duct stem cells, but focus on the adult mouse and fetal human gallbladders. We were able to successfully isolate and expand a resident epithelial stem cell from adult mouse gallbladder and intrahepatic bile duct system. Furthermore, we show that these cells are distinct or unique from each other. In addition, we have identified cell surface markers that can be used for the prospective isolation of candidate fetal human gallbladder stem cells and have determined that these cells have distinct phenotypic profiles compared to intrahepatic bile duct cells. Last, we identified candidate transcription factors that can be used for the reprogramming of gallbladder stem cells into hepatocytes. These experiments set the stage for future studies that could have important ramifications for cell-based therapy for liver disease.
Author: Rohan Manohar
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W206237825