University of Illinois Urbana-Champaign

Engineered 3D microenvironments to understand and direct liver progenitor and cancer cell fate

Gentile, Stefan Dell

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GENTILE-DISSERTATION-2019.pdf

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https://hdl.handle.net/2142/106454

Description

Title
Engineered 3D microenvironments to understand and direct liver progenitor and cancer cell fate
Author(s)
Gentile, Stefan Dell
Issue Date
2019-12-04
Director of Research (if dissertation) or Advisor (if thesis)
Underhill, Gregory H
Doctoral Committee Chair(s)
Underhill, Gregory H
Committee Member(s)
  • Wagoner Johnson, Amy J
  • Kong, Hyunjoon
  • Perez-Pinera, Pablo
Department of Study
Bioengineering
Discipline
Bioengineering
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2020-03-02T22:38:45Z
Keyword(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.
Graduation Semester
2019-12
Type of Resource
text
Permalink
http://hdl.handle.net/2142/106454
Copyright and License Information
Copyright 2019 Stefan Gentile

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