When: April 26, 2017, 2:00 pm
Location: 3rd Floor Orchard View Room , Discovery Building
Contact: 608-316-4401, firstname.lastname@example.org
Directed differentiation of human pluripotent stem cells to blood-brain barrier endothelial cells
The blood-brain barrier (BBB) is comprised of specialized endothelial cells that are critical to neurological health. A key tool for understanding human BBB development and its role in neurological disease is a reliable and scalable source of functional brain microvascular endothelial cells (BMECs). Human pluripotent stem cells (hPSCs) can theoretically generate unlimited quantities of any cell lineage in vitro, including BMECs, for disease modeling, drug screening and cell-based therapies. Here, we demonstrate a facile, chemically-defined method to differentiate hPSCs into BMECs in a developmentally relevant progression via small molecule activation of key signaling pathways. hPSCs are first induced to mesoderm commitment by activating canonical Wnt signaling. Next, these mesoderm precursors progress to endothelial progenitors, and treatment with retinoic acid (RA) leads to acquisition of BBB-specific markers and phenotypes. hPSC-derived BMECs generated via this protocol exhibit endothelial properties, including tube formation and LDL uptake, as well as efflux transporter activities characteristic of BMECs. Notably, these cells exhibit high transendothelial electrical resistance (TEER), above 3000 Ω•cm2. These hPSC-derived BMECs serve as a robust human in vitro BBB model that can be used to study brain disease and inform therapeutic development.
Bio: PhD, Biomedical Engineering, Peking University, Beijing China, and MD degree, Shanghai Jiao Tong University, Shanghai, China, Have been in Madison for a little bit over three years in Sean Palecek & Eric Shusta’s Chemical and Biological Engineering lab doing stem cell research. Mainly focus on blood-brain barrier (BBB) endothelial cell differentiation. I also have several side projects, including shear stress role in BBB development, stem cell differentiation into other cell lineages.
All QBio sponsored talks take place on Wednesdays at 2:00 p.m. in the 3rd floor Orchard View room of the Discovery Building unless otherwise noted. Talks are open to the public. Access to the room is via the elevator behind Aldo’s Cafe in the Northeast corner of the building.