Date of Award
8-1-2024
Degree Name
Doctor of Philosophy
Department
Engineering Science
First Advisor
Chowdhury, Farhan
Abstract
Embryonic stem cell (ESC) research has profoundly impacted our comprehension of developmental biology and significantly advanced the field of regenerative medicine since its inception. Traditionally, the cultivation of stem cells is heavily dependent on exogenous chemical factors such as leukemia inhibitory factors or a combination of inhibitors and activators to either sustain self-renewal or direct differentiation. These methods, while effective, are not without limitations, as ESCs often exhibit sporadic differentiation or loss of pluripotency under these conditions. Recent advances in the field highlight the pivotal role of mechanical cues from the extracellular matrix (ECM) in modulating stem cell fate, akin to other cell types that respond to their mechanical environment. Despite this recognition, many stem cell studies continue to overlook the integration of mechanical stimuli in experimental setups. This dissertation underscores the significance of engineering the surface chemistry and rheological properties of culture substrates to manipulate ESC behavior, maintaining naïve pluripotency, directing differentiation, or reversing more differentiated epiblast stem cells to an ESC-like state without reliance on chemical supplements. Our findings suggest that mechanical and chemical cues do not act independently but rather in synergy, significantly influencing stem cell fate decisions.
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