12th Symposium of the European Society of Biochemical Engineering Sciences

Biomanufacturing Cardiovascular Cells from Human Pluripotent Stem Cells

 

Prof. Sean Palecek

Professor in the Department of Chemical & Biological Engineering at the University of Wisconsin – Madison

 

Human pluripotent stem cells (hPSCs) offer tremendous promise as a source of regenerative therapeutic cells since they have virtually unlimited proliferative capacity and the ability to differentiate to any cell type found in the body.  Advances in cellular biomanufacturing are needed to produce large quantities of safe and potent cells at a reasonable cost as hPSCs move toward clinical applications.  For example, approximately 109 cells would be needed to replace the cardiac cells lost during a typical myocardial infarction. Ideally these cells would be produced in suspension culture under defined, xeno-free conditions.  I will discuss recent advances in using small molecules and growth factors to guide hPSCs through cardiac progenitors to a variety of cardiac cell types, including cardiomyocytes, endothelial cells, epicardial cells, endocardial cells, smooth muscle cells, and cardiac fibroblasts.  Activation of canonical Wnt signaling drives hPSCs to mesoderm progenitors and subsequent inhibition of the Wnt pathway specifies multipotent cardiac progenitors.  Through screening approaches and media optimization, we identified protein-free culture conditions under which these cardiac progenitors can form cardiomyocytes at a media cost of approximately $1 per 106 cells.  Alternatively, reactivation of Wnt signaling pushes the cardiac progenitors to epicardial cells which can then be further differentiated to smooth muscle cells, cardiac fibroblasts, and endothelial cells using specific growth factors.  These advances in cardiac cell manufacturing enable production of large quantities of high quality cardiac cells and tissues for in vitro studies, drug screening and toxicology, and development of cell-based therapies to treat heart disease.