Controlled Drug Release with Ultrasound Imaging Monitoring Capability

Over the past decade tremendous progress has been made in developing processes to direct the differentiation of human pluripotent stem cells to various specialized cell types for a variety of applications including development and disease modeling, drug screening and evaluation, and regenerative therapeutics. Typically these approaches involve construction of biomimetic microenvironments to guide stem cell differentiation in a developmentally-relevant manner. However, these approaches are often costly, inefficient, difficult to scale, and not compatible with cGMP manufacturing. The next generation of differentiation platforms requires simple, robust, inexpensive, and xeno-free characteristics. In this presentation I will discuss evolution of differentiation platforms for cardiovascular. We have identified canonical Wnt signaling as a key regulator of hPSC differentiation to cardiomyocyte 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 a different canonical Wnt signaling profiles can direct hPSCs to vascular endothelial progenitors and epicardial cells in a defined, growth factor-free differentiation process. These epicardial cells can give rise to cardiac fibroblasts and smooth muscle cells upon induction of an epithelial-to-mesenchymal transition. Thus, by stage-specific modulation of canonical Wnt signaling and other developmental pathways we can generate a diverse array hPSC-derived cardiac cells in defined, xeno-free conditions for in vitro studies, drug screening and toxicology analyses, and development of regenerative therapies.