All ETDs from UAB

Advisory Committee Chair

Andra R Frost

Advisory Committee Members

Douglas Hurst

Joel Berry

Joanne Murphy-Ullrich

Rosa Serra

Document Type

Dissertation

Date of Award

2017

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Tumors are three dimensional tissues consisting of malignant cells and various stromal cell populations within a volume of extracellular matrix. These components form an intricate network that influences many facets of tumor biology. Paracrine interactions between tumor cells and the surrounding microenvironment can alter drug response and impact therapeutic efficacy in vivo, yet most current in vitro models do not accurately recapitulate the stromal microenvironment or associated dimensionality of human tumors. In vitro models that are more representative of the human tumor microenvironment, including a more recapitulative dimensionality and cellular composition, have broad utility in the evaluation of mechanisms driving cancer progression, therapeutic efficacy, and therapeutic resistance/tumor recurrence. Representative models are challenging to construct in vitro; therefore, most current models do not accurately mimic the dimensionality, structure, or stromal microenvironment of human tumors. Herein, we aim to develop novel tissue engineered in vitro surrogates of breast carcinoma. These surrogates will include malignant breast epithelial cells and breast cancer associated fibroblasts within a three dimensional volume of extracellular matrix that approximates the sizes of many human breast cancers at diagnosis. Microchannels engineered within the breast carcinoma surrogates will be continuously perfused with nutrients via a bioreactor platform to promote cell viability and growth throughout culture. The utility of these surrogates in the prediction of therapeutic response will be assessed and non-destructive methods to evaluate the engineered surrogates during culture will be

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