Description
- Abstract:
- The placenta plays a crucial role during pregnancy, yet it remains one of the least understood human organs. Trophoblast cells comprise the placenta with functions including nutrient and waste transport, invading the endometrium to anchor the placenta, and remodeling vasculature for adequate blood flow. These placental trophoblast cells have great potential for use in developing non-invasive prenatal testing and in vitro models of the maternal-fetal interface. In this thesis we utilized biomaterial and diagnostic techniques to (1) develop a rapid and inexpensive method for enriching trophoblast cells from clinical cervical samples for non-invasive prenatal testing, (2) develop lipid models representative of trophoblast cells at various gestational time points, and (3) consider therapeutic design of pharmaceuticals for improving drug efficacy with the potential to mitigate placental interaction. Our enrichment method led to an ~700% enrichment of trophoblast cells from cervical samples with the ability to then isolate a single trophoblast cell using automated cell picking. Our in vitro trophoblast lipid models mimic 1st, 3rd, and full-term trophoblasts and were used to study antifungal pharmaceutical and environmental toxicant interactions. Additionally, we contributed to the fundamental lipid bilayer field through studies focusing on the role of flow on rupturing vesicles into supported lipid bilayers and investigating phthalate interactions with lipid structures. Finally, we developed antifungal nanoparticles by encapsulating the antifungal therapeutic, anidulafungin, into liposomes, also for future use by pregnant women that are prone to fungal infections. These nanoparticles demonstrated increased efficacy against planktonic and biofilm Candida albicans while also improving survival of Candida infected Galleria mellonella compared to free drug. Ultimately, this thesis provides new methods to understand and use trophoblast cells for the improvement of maternal and fetal health. The biotechnological approaches we have developed have the ability to minimize risk to a developing fetus, enable better informed treatment plans, and allow for screening of new therapies.
- Notes:
- Thesis (Ph. D.)--Brown University, 2020
Access Conditions
- Rights
- In Copyright
- Restrictions on Use
- All rights reserved. Collection is open to the Brown community for research.
Citation
Bailey-Hytholt, Christina Mary,
"Using Trophoblast Cells to Develop Biotechnological Approaches that Advance Prenatal and Women’s Health"
(2020).
Biomedical Engineering Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:1129456/
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Biomedical Engineering Theses and Dissertations
Theses and Dissertations for the Biomedical Engineering department....