Date of Award

2019-01-01

Degree Name

Doctor of Philosophy

Department

Engineering

Advisor(s)

Thomas . Boland

Abstract

Current breast cancer treatments are successful in eradicating this disease in the majority of patients, though there are quite a few cases where relapse or recurrence follow, which may lead to continued cancer therapy or death. Thermal inkjet bioprinting (BP) is a novel technique that is used to bioprint biomaterials or diverse cellular organisms to engineer tissue or organ models in vitro. In this Dissertation, we investigated the molecular effect of BP MCF7 breast cancer cells (BCC), cell survival of the cells when exposed to FDA approved systemic therapy alone and in combination with radiation and lastly, the ability of the cells to form tumors in immunodeficient mice. In the Phospho-MAPK array, a total of 21 kinases were phosphorylated in the BP MCF7 cells, whereas 9 were phosphorylated in the manually seeded controls. The RNA sequence analysis of the BP MCF7 cells identified a total of 12,235 genes, of which 9.7% were statistically differentially expressed. Using a q-value � 0.05 and a ± 2 fold change as the cutoff value for the number of upregulated and downregulated genes, a total of 266 and 206 respectively were observed, with 5 genes uniquely expressed in the BP cells: NRN1L, LUCAT1, IL6, CCL26, and LOC401585. When Bioprinted MCF7 BCCs were challenged with Tamoxifen, we observed an 8-10% cell viability higher than MS BCCs at 10µM, 90µM and 110µM concentrations with a statistical significance and similar results were obtained when cells were exposed to palbociclib + letrozole at 10µM, 50µM, 100µM and 150µM. Statistical significance was observed at 10µM, 100µM and 150µM concentrations of palbociclib, p < .05. Results from the tissue we analyzed of the implanted BP MCF7 BCCs appeared to contain some hyperplasia with carcinoma in situ, whereas in the tissue from the manually seeded implants we were unable to identify cancerous cells. In the phosphoMAPK array, bioprinted MCF7 cells showed increased levels of phosphorylation in analytes that have been identified as key players in activating critical pathways that, when dysregulated, are associated with biological aggressive oncogenic properties. RNA data suggest that thermal inkjet bioprinting is stimulating large scale gene alterations that could potentially be used for drug discovery. These biological investigations will change the approach to future drug discovery in vitro when applying thermal inkjet bioprinting. Furthermore, this technique could also be applied to bioprint autologous samples nor only with MCF7 breast cancer cells but with any other cancer cells to predict with higher certainty whether a potential treatment regimen will work effectively in cancer patients.

Language

en

Provenance

Received from ProQuest

File Size

147 pages

File Format

application/pdf

Rights Holder

Aleli Campbell

Available for download on Wednesday, July 22, 2020

Included in

Biomedical Commons

Share

COinS