Microenvironmental Regulation of Oval Cell Functions

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DESCRIPTION (provided by applicant): Hepatic oval cells are an intriguing potential cell source for liver tissue engineering and other cell-based liver therapies due to their ability to be expanded in culture and their bipotential differentiation into hepatocytes or bile duct epithelial cells. However, many aspects of oval cell bjology, in particular, the regulation of oval cell responses by microenvironmental factors, remain undefined. The proposed research will utilize a model system based on photopolymerized hydrogels to investigate oval cell functions in 2-D and 3-D settings. Specifically, these experiments will examine the role of integrins and Notch receptors in specifying oval cell fate processes such as adhesion, migration, and signaling. Photopatterned hydrogel platforms will be utilized to investigate the effect of asymmetric presentation of external cues, and cross-talk between integrins and Notch will also be assessed. These studies will provide fundamental insight into oval cell responses, important for the development of tissue engineered liver therapies. The controlled incorporation of important regulators of oval cell functions in 3-D and/or asymmetrically represents an important advancement towards an oval cell-based tissue engineered liver construct.