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Title:Engineered 3D microenvironments to understand and direct liver progenitor and cancer cell fate
Author(s):Gentile, Stefan Dell
Director of Research:Underhill, Gregory H
Doctoral Committee Chair(s):Underhill, Gregory H
Doctoral Committee Member(s):Wagoner Johnson, Amy J; Kong, Hyunjoon; Perez-Pinera, Pablo
Department / Program:Bioengineering
Discipline:Bioengineering
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Engineered systems
Bioengineering
Microenvironment
Extracellular matrix
Hydrogel
Cellular microarray
High-throughput
Confocal microscopy
Flow cytometry
Image cytometry
Liver progenitor
Liver development
Hepatoblast
Hepatocyte
Cholangiocyte
Biliary
TGFβ1
Cell spheroid
3D aggregates
Hydrogel particles
Liver cancer
Hepatocellular carcinoma
Tumor microenvironment
3D cancer culture
Cancer co-culture
Microwell array
Drug response
Hepatic stellate cells
Portal fibroblasts
Collagen
Abstract:The cellular microenvironment encompasses every chemical and physical factor surrounding a cell, including all other cells, cell-cell and cell-extracellular matrix (ECM) signaling interactions and any detectible change in conditions. As the interplay between every component of the microenvironment synergistically or antagonistically leads to changes in cell function and fate, the use of engineered systems allows for deconstruction of the various cues to understand the roles that they play in cell behavior and to understand how these cues can be used to modulate cell fate. Often these systems take the form of in vitro 2D monolayer cell culture, but there is a concerted effort to integrate 3D engineered systems in cell fate determination studies due to their more in vivo-like structure and the significant changes in microenvironmental cues they provide. In this dissertation, I describe two different 3D engineered systems to examine different processes within the liver. One system was designed to examine liver progenitor development and integrate tunable factors that can be used to change the differentiation trajectory of these progenitors in a 3D aggregate. We found them to be very susceptible to the growth factor TGFβ1 and the introduction of polymer microparticles to push differentiation towards a desired fate. The other system utilized a tunable microarray system to create geometrically controlled hepatocellular carcinoma spheroids and 3D cancer co-culture spheroids with relevant niche cells, showing how manipulating the aggregate size, shape and potential co-culture changed cell behavior and fate. Together, these 3D engineered systems present different methods of deconstructing and manipulating microenvironmental cues to produce targeted cell fate changes within two different aspects of the liver, with many potential uses in other liver and non-liver specific processes.
Issue Date:2019-12-04
Type:Text
URI:http://hdl.handle.net/2142/106454
Rights Information:Copyright 2019 Stefan Gentile
Date Available in IDEALS:2020-03-02
Date Deposited:2019-12


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