BME Seminar Series: Simple and robust strategies for biomanufacturing of cardiac cells from human pluripotent stem cells
November 26, 2018 @ 12:00 pm - 1:00 pm
Sean Palecek, Ph.D.; Professor of Chemical and Biological Engineering at University of Wisconsin-Madison
Stem cells process numerous cues in their environment in making discrete fate choices, including differentiation to specialized cell types. Immobilized extracellular matrix cues, soluble signals, cell-cell communication, and mechanical signals have all been shown to affect self-renewal and differentiation. Realization of the scientific and therapeutic potential of stem cells requires the ability to reliably produce large quantities of high-quality cells by controlling stem cell differentiation in vitro. While developmental biology provides a template for designing differentiation processes, recapitulation of the environment in a developing organ in a bioreactor may be too complex to be effective. I will discuss examples that illustrate how precise temporal orchestration of a small number of developmental pathways using soluble factors can guide human pluripotent stem cell (hPSC) differentiation to various cardiac lineages. For example, we have identified canonical Wnt signaling as a key regulator of cardiomyocyte differentiation and designed a protocol that produces high purity cardiomyocytes in a defined, xeno-free, growth factor-free system via appropriate temporal presentation of small molecule modulators of Wnt signaling. Furthermore, we have determined that specific canonical Wnt activation and inhibition profiles combined with TGFβ superfamily or VEGF ligands can direct hPSCs to vascular endothelial progenitors, epicardial cells, cardiac fibroblasts, smooth muscle cells, and endocardial cells in defined processes. I will also discuss the challenges of quality control in monitoring differentiation and maturation states of hPSC-derived cardiovascular cells via marker expression and phenotypes. Thus, by stage-specific modulation of signaling pathways that regulate heart development in vivo, we can generate hPSC-derived cardiac cells for in vitro studies, drug screening and toxicology analyses, and development of regenerative therapies.