Theses and Dissertations
This collection includes both ASU Theses and Dissertations, submitted by graduate students, and the Barrett, Honors College theses submitted by undergraduate students.
Filtering by
- All Subjects: Stem Cells
- Creators: Harrington Bioengineering Program
Advances in cellular reprogramming, have enabled the generation of in vitro disease models that can be used to dissect disease mechanisms and evaluate potential therapeutics. To that end, efforts by many groups, including the Brafman laboratory, to generated patient-specific hiPSCs have demonstrated the promise of studying AD in a simplified and accessible system. However, neurons generated from these hiPSCs have shown some, but not all, of the early molecular and cellular hallmarks associated with the disease. Additionally, phenotypes and pathological hallmarks associated with later stages of the human disease have not been observed with current hiPSC-based systems. Further, disease relevant phenotypes in neurons generated from SAD hiPSCs have been highly variable or largely absent. Finally, the reprogramming process erases phenotypes associated with cellular aging and, as a result, iPSC-derived neurons more closely resemble fetal brain rather than adult brain.
It is well-established that in vivo cells reside within a complex 3-D microenvironment that plays a significant role in regulating cell behavior. Signaling and other cellular functions, such as gene expression and differentiation potential, differ in 3-D cultures compared with 2-D substrates. Nonetheless, previous studies using AD hiPSCs have relied on 2-D neuronal culture models that do not reflect the 3-D complexity of native brain tissue, and therefore, are unable to replicate all aspects of AD pathogenesis. Further, the reprogramming process erases cellular aging phenotypes. To address these limitations, this project aimed to develop bioengineering methods for the generation of 3-D organoid-based cultures that mimic in vivo cortical tissue, and to generate an inducible gene repression system to recapitulate cellular aging hallmarks.
Lab-grown food products of animal cell origin, now becoming popularly coined as, ‘Cellular Agriculture’ is a revolutionary breakthrough technology that has the potential to penetrate the lives of every American or citizen of the world. It is important to recognize that the impetus for developing this technology is fueled by environmental concerns with climate change, rising geopolitical instability, and population growth projections, where farm-grown food has now become a growing national security issue. Notwithstanding its potential, in addition to the necessary technological innovation and economic scalability, the market success of cellular agriculture will depend greatly on regulatory oversight by multiple government agencies without which it can cause undue harm to individuals, populations, and the environment. Thus, it is critical for those appropriate United States governing bodies to ensure that the technology being developed is both safe and of an acceptable quality for human consumption and has no adverse environmental impact. As such, animal foods, derived from farms, previously regulated almost exclusively by the United States Department of Agriculture (USDA) are now being regulated under a joint formal agreement between the US Food and Drug Administration (US FDA) and the USDA if derived from the lab, i.e., lab-grown animal foods. The main reason for joint oversight between the FDA and the USDA is that the FDA has developed the in-house expertise to oversee primary cell harvesting and cell storage, as well as, cell growth and differentiation for the development of 3D-engineered tissues intended for tissue and organ replacement for the emerging field of regenerative medicine. As such, the FDA has been given the authority to oversee the ‘front end’ of lab-grown food processes which relies on the very same processes utilized in engineered human tissues to produce food-grade engineered tissues. Oversight then transitions to the USDA-FSIS (Food Safety and Inspection Service) during the harvesting stage of the cell culture process. The USDA-FSIS then oversees the further production and labeling of these products. Included in the agreement is the understanding that both bodies are responsible for communicating necessary information to each other and collaboratively developing new regulatory actions as needed. However, there currently lacks clarity on some topics regarding certain legal, ethical, and scientific issues. Lab-grown meat products require more extensive regulation than farm-grown animal food products to ensure that they are safe and nutritious for consumption. To do this, CFSAN can create new classes of lab-grown foods, such as ‘lab-grown USDA foods,’ ‘lab-grown non-USDA foods,’ ‘lab-grown extinct foods,’ ‘lab-grown human food tissues,’ and ‘medically activated lab-grown foods.’