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Benjamin Gastfriend, Research Assistant, Chemical & Biological Engineering (Shusta/Palecek labs), “Modeling blood-brain barrier development and function with stem cell-derived brain endothelial cells and pericytes”
November 20, 2018 @ 12:00 pm - 1:00 pm
Topic: Modeling blood-brain barrier development and function with stem cell-derived brain endothelial cells and pericytes
Abstract: The blood-brain barrier (BBB) regulates the transport of ions, molecules, and cells between blood and brain, and as such plays a vital role in maintaining brain heath. The BBB represents a significant impediment to brain drug delivery, and is compromised in many neurological diseases. While brain microvascular endothelial cells (BMECs) form the BBB, several other brain cell types including astrocytes, neurons, and pericytes play key roles in BBB development and function and together form an integrated neurovascular unit (NVU). The molecular cues mediating this regulation remain incompletely characterized. Multicellular in vitro models of the NVU derived from human pluripotent stem cells (hPSCs) are scalable, high fidelity, and applicable not only to drug permeability screening, but also to the discovery of molecular mechanisms important in BBB development and disease. Existing hPSC-based NVU models lack the important contribution of brain pericytes, cells that line the outer wall of microvessels and are required for BBB formation and maintenance. Here we show that brain pericyte-like cells can be differentiated from hPSCs through a neural crest progenitor, and that these brain pericyte-like cells have relevant molecular and phenotypic properties. Importantly, when co-cultured with hPSC-derived BMECs, these pericyte-like cells enhance several relevant barrier characteristics in BMECs. Finally, we discuss ongoing work employing these hPSC-derived pericyte-like cells to better understand molecular mechanisms of brain pericyte development and BMEC-pericyte interactions.