“Engineering Improvements in the Quality of Stem Cell-Derived Cardiovascular Cells”
Hosted by the Department of Biomedical Engineering (BME)
Abstract: The past decade has seen tremendous advances in development of processes to efficiently differentiate human pluripotent stem cells (hPSCs) to somatic cell types by directing the cells through developmental stages. These hPSC-derived cells enable study of human development and disease, drug screening and toxicology, and open the door to cell-based regenerative therapies. However, these hPSC-derived cells often lack key quality attributes found in adult cells, limiting their use as a human model. For example, hPSC-derived cardiomyocytes exhibit structural and functional hallmarks of fetal cardiomyocytes, but do not approach electromechanical properties of adult cardiomyocytes. Furthermore, achieving tissue level structure and function has been achieved by organoids in some tissues, such as intestinal and cerebral. Other organoids, including cardiac, remain elusive.
In this seminar I will describe our recent efforts to assess and improve cardiomyocyte maturation using cues generated by other cardiac cell types at the appropriate developmental stage. We have developed efficient methods to differentiate hPSCs to endothelial cells, epicardial cells, and cardiac fibroblasts. Simple co-culture models indicate that hPSC-derived epicardial cells increase proliferation and impede maturation of early stage hPSC-derived cardiomyocytes, while hPSC-derived endothelial cells and cardiac fibroblasts accelerate acquisition of some structural and functional phenotypes associated with cardiomyocyte maturity. In addition, we have used multi-omics approaches to profile hPSC-derived cardiomyocytes during extended culture and identified both intracellular and extracellular metabolites and pathways associated with maturation. We envision that monitoring these metabolites have the potential to serve as quality attributes during manufacturing of hPSC-derived cardiomyocytes.
Bio: Sean Palecek is the Milton J. and Maude Shoemaker Professor and Vilas Distinguished Achievement Professor in the Department of Chemical & Biological Engineering at the University of Wisconsin – Madison. Sean is the Bioengineering Thrust Leader for the UW Stem Cell and Regenerative Medicine Center, the Director for Research for the National Science Foundation Center for Cell Manufacturing Technologies (CMaT), and the Director for Research Innovation for the Forward BIO Institute. Sean is also a Fellow at the Allen Institute for Cell Science. Sean’s research lab studies how human pluripotent stem cells (hPSCs) sense and respond to microenvironmental cues in making fate choices, with a focus on differentiation to cardiovascular lineages. Sean’s lab has generated novel mechanistic insight and developed protocols for differentiation of hPSCs to cardiovascular and neurovascular cell types. They strive to engineer fully-defined, animal component-free differentiation platforms, compatible with biomanufacturing of cells and tissues for in vitro and in vivo diagnostic and regenerative medicine applications.
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