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Isolation and Expansion of a unique stem cell population from human and mouse gallbladders

Manohar, Rohan (2012) Isolation and Expansion of a unique stem cell population from human and mouse gallbladders. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Manohar, Rohanrrm19@pitt.eduRRM19
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorLagasse, EricLagasse@pitt.eduLAGASSE
Committee ChairMichalopoulos, GKmichalopoulosgk@upmc.eduMICHAL
Committee MemberFox,
Committee MemberStrom, Stephen C.strom@pitt.eduSTROM
Committee MemberDemetris, AJdemetrisaj@upmc.eduDEMETRIS
Committee MemberOrwig, Kyleorwigke@upmc.eduKEO6
Date: 9 August 2012
Date Type: Publication
Defense Date: 12 April 2012
Approval Date: 9 August 2012
Submission Date: 26 July 2012
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 135
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Cellular and Molecular Pathology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: gallbladder, liver, stem cells, hepatocytes, Intrahepatic bile duct cells
Date Deposited: 09 Aug 2012 14:38
Last Modified: 19 Dec 2016 14:38


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