Master's Theses

Date of Award

2017

Document Type

Thesis

Department

Biomedical Engineering

First Advisor

Sihong Wang

Keywords

fibroblasts, microfluidic cell array, cancer, 3D, Matrigel

Abstract

Modeling an accurate depiction of the tumor microenvironment, (TME), is essential to observe the effect external factors might have on the tumor in vivo. In cancer therapy specifically, the outcomes of clinical treatments are heavily dependent on drug testing methods despite the cytotoxic effects these methods might have on the patient. Our lab has previously developed a three layered microfluidic cell array (3D μFCA) to reconstruct the relevantly spatial configuration of tumor and microvasculature found in vivo in order to develop a more efficient tool of high throughput drug discovery and screening. In this study, we optimized this device to include a vital component found in tumor stroma, fibroblasts, and conducted proliferation, metabolic and drug response studies to investigate the effects of fibroblast on drug responses. We found that healthy fibroblasts reduces triple negative breast cancer cell proliferation in the 2D coculture, but the cancer cell growth rate increases in the 3D static and device coculture. Additionally, preliminary quantitative image analysis showed that the coculture condition had lower apoptosis indicated by caspase-3 activity after Doxorubicin introduction compared to the control condition. With these findings, we can gain a better understanding into the effects of drugs on tumors in vivo through in vitro methods to provide a platform of accurate drug screening.

 
 

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