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Thesis
The design of a novel 3D micropatterned tumor microenvironment model to study the intercellular effects of fibroblasts and cancer cells
Master of Science (M.S.), Drexel University
Aug 2013
DOI:
https://doi.org/10.17918/etd-4471
Abstract
The tumor microenvironment contains a multitude of biomolecules, stromal cells such as fibroblasts, endothelial cells, inflammatory cells, and signaling molecules that support the tumor's growth and progression. Particularly around the site of tumors, fibroblasts are "primed" to adopt a myofibroblastic phenotype, and are known as cancer associated fibroblasts (CAFs) that promote tumor growth and progression instead of aiding the body. Much interest has been taken in the individual cellular interactions between tumor cells and the surrounding cancer-associated fibroblasts. Systems are constantly being designed to better emulate the complex internal environment around the tumor in order to understand how the tumor stroma communicates and affects the tumor growth. In this thesis, a 3D microenvironment model was developed that simulates the native extracellular matrix and allows for the study of individual cellular interactions between cancer cells and fibroblasts, particularly those involving transmission of cell-generated contractile forces. The final system design in brief involves spatially constraining MDA-MB-231 human breast adenocarcinoma cells and human dermal fibroblasts on fibronectin micropatterns on a polydimethylsiloxane (PDMS) substrate. A poly-L-lysine/glutaraldehyde treated PDMS gasket was placed around the cells, and a collagen overlay was added, to allow cells to interact with a 3D environment. Live cell microscopy was used to track cell movement over time, and the images were analyzed with MATLAB. Additionally, a protocol for differentiating myofibroblasts was optimized for the inclusion into the system. The significance of this study is that it offers a novel 3D cell culture system that boasts of the ability for control over individual cell positions in order to observe the effects of fibroblasts and cancer cells in a 3D environment that resembles the in vivo environment more than that of the standard 2D culture system.
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Details
- Title
- The design of a novel 3D micropatterned tumor microenvironment model to study the intercellular effects of fibroblasts and cancer cells
- Creators
- Christine Maylin Ho - DU
- Contributors
- Adrian C. Shieh (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 4471; 991014632315304721