Stems cells differentiate into specialized cells and are a focal point for treatments related to injured tissue. These treatments require understanding of how stem cells differentiate into the types of cells and tissues that are needed at the site of injury. Heart disease, which is the leading cause of death in the United States, may be treated by generating cardiac tissue from induced pluripotent stem cells (iPSCs). In this project, fatty acids will be delivered into iPSCs to stimulate them to differentiate and mature into cardiac cells and tissues. The hypothesis is that precise control of fatty acid delivery could cause the cells to mimic the natural developmental pathway. If successful, such control could potentially lead to the development of new approaches for tissue and organ regeneration. Project-based learning activities will engage elementary school students' interest in science. This will nurture their interest in STEM topics lasting throughout their education as well as influence their career decisions as adults.
Genomic sequencing and high-throughput screening have enhanced our ability to understand specific intracellular responses and regulatory pathways. Novel experimental designs are needed to address the complex responses to various biological modulators of cells, leading to tissue specification and lineage commitment. There is a metabolic switch from glycolysis to oxidative phosphorylation during cardiac development. Recently, a link between energy metabolism and cell signaling and epigenetic regulation of gene expression has been established. As a result, efficient delivery of fatty acids that participate in the oxidative phosphorylation cycle could be a powerful tool to exercise fine control over gene expression. This project will utilize a unique microfluidic device to deliver fatty acids into the cytoplasm of induced pluripotent stem cells (iPSCs). This should direct their differentiation and maturation to cardiac lineages. The investigators hypothesize that precise control over fatty acid availability will metabolically switch iPSCs from glycolysis to oxidative phosphorylation and thereby consistently mimic the native developmental, metabolic conditions necessary for cardiac differentiation and maturation. This project will play a key role in the scalability of iPSC-derived cells in future clinical applications as well as potentially lead to the development of new paradigms for metabolic induced tissue and organ regeneration.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
