Author ORCID Identifier

https://orcid.org/0000-0002-0760-8196

Defense Date

2018

Document Type

Thesis

Degree Name

Master of Science

Department

Biomedical Engineering

First Advisor

Rebecca Heise, PhD

Second Advisor

Angela Reynolds, PhD

Third Advisor

Christopher Lemmon, PhD

Abstract

COPD is characterized by tissue inflammation and impaired remodeling that suggests fibroblast maintenance of structural homeostasis is dysregulated. Thus, we performed in vitro wound healing experiments on normal and diseased human lung fibroblasts and developed an ABM of fibroblasts closing a scratched monolayer using NetLogo to evaluate differences due to COPD or cigarette smoke condensate exposure. This ABM consists of a rule-set governing the healing response, accounting for cell migration, proliferation, death, activation and senescence rates; along with the effects of heterogeneous activation, phenotypic changes, serum deprivation and exposure to cigarette smoke condensate or bFGF. Simulations were performed to calibrate parameter-sets for each cell type using in vitro data of scratch-induced migration, viability, senescence-associated beta-galactosidase and alpha-smooth muscle actin expression. Parameter sensitivities around each calibrated parameter-set were analyzed. This model represents the prototype of a tool designed to explore fibroblast functions in the pathogenesis of COPD and evaluate potential therapies.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-10-2018

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