Biomaterial Database

Defined Differentiation of Human Pluripotent Stem Cells to Brain Microvascular Endothelial-Like Cells for Modeling the Blood-Brain Barrier. 2023

Koji L Foreman, and Eric V Shusta, and Sean P Palecek

Department of Chemical and Biological Engineering, Department of Neurological Surgery, University of Wisconsin-Madison, Madison, WI, USA.

The blood-brain barrier (BBB) comprises brain microvascular endothelial cells (BMECs) that form a high-resistance cellular interface that separates the blood compartment from the brain parenchyma. An intact BBB is pivotal to maintaining brain homeostasis but also impedes the entry of neurotherapeutics. There are limited options for human-specific BBB permeability testing, however. Human pluripotent stem cell models offer a powerful tool for dissecting components of this barrier in vitro, including understanding mechanisms of BBB function, and developing strategies to improve the permeability of molecular and cellular therapeutics targeting the brain. Here, we provide a detailed, step-by-step protocol for differentiation of human pluripotent stem cells (hPSCs) to cells exhibiting key characteristics of BMECs, including paracellular and transcellular transport resistance and transporter function that enable modeling the human BBB.

UI	MeSH Term	Description	Entries
D001812	Blood-Brain Barrier	Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.	Brain-Blood Barrier,Hemato-Encephalic Barrier,Barrier, Blood-Brain,Barrier, Brain-Blood,Barrier, Hemato-Encephalic,Barriers, Blood-Brain,Barriers, Brain-Blood,Barriers, Hemato-Encephalic,Blood Brain Barrier,Blood-Brain Barriers,Brain Blood Barrier,Brain-Blood Barriers,Hemato Encephalic Barrier,Hemato-Encephalic Barriers
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D002454	Cell Differentiation	Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.	Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D042783	Endothelial Cells	Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.	Capillary Endothelial Cells,Lymphatic Endothelial Cells,Vascular Endothelial Cells,Capillary Endothelial Cell,Cell, Capillary Endothelial,Cell, Endothelial,Cell, Lymphatic Endothelial,Cell, Vascular Endothelial,Cells, Capillary Endothelial,Cells, Endothelial,Cells, Lymphatic Endothelial,Cells, Vascular Endothelial,Endothelial Cell,Endothelial Cell, Capillary,Endothelial Cell, Lymphatic,Endothelial Cell, Vascular,Endothelial Cells, Capillary,Endothelial Cells, Lymphatic,Endothelial Cells, Vascular,Lymphatic Endothelial Cell,Vascular Endothelial Cell
D057026	Induced Pluripotent Stem Cells	Cells from adult organisms that have been reprogrammed into a pluripotential state similar to that of EMBRYONIC STEM CELLS.	Human Induced Pluripotent Stem Cell,IPS Cell,IPS Cells,Induced Pluripotent Stem Cell,Fibroblast-Derived IPS Cells,Fibroblast-Derived Induced Pluripotent Stem Cells,Human Induced Pluripotent Stem Cells,hiPSC,Cell, Fibroblast-Derived IPS,Cell, IPS,Cells, Fibroblast-Derived IPS,Cells, IPS,Fibroblast Derived IPS Cells,Fibroblast Derived Induced Pluripotent Stem Cells,Fibroblast-Derived IPS Cell,IPS Cell, Fibroblast-Derived,IPS Cells, Fibroblast-Derived
D039904	Pluripotent Stem Cells	Cells that can give rise to cells of the three different GERM LAYERS.	Stem Cells, Pluripotent,Pluripotent Stem Cell,Stem Cell, Pluripotent