Abstract
Brain pericytes play important roles in the formation and maintenance of the neurovascular unit (NVU), and their dysfunction has been implicated in central nervous system disorders. While human pluripotent stem cells (hPSCs) have been used to model other NVU cell types, including brain microvascular endothelial cells (BMECs), astrocytes, and neurons, hPSC-derived brain pericyte-like cells have not been integrated into these models. In this study, we generated neural crest stem cells (NCSCs), the embryonic precursor to forebrain pericytes, from hPSCs and subsequently differentiated NCSCs to brain pericyte-like cells. These cells closely resembled primary human brain pericytes and self-assembled with endothelial cells. The brain pericyte-like cells induced blood-brain barrier properties in BMECs, including barrier enhancement and reduced transcytosis. Last, brain pericyte-like cells were incorporated with iPSC-derived BMECs, astrocytes, and neurons to form an isogenic human model that should prove useful for the study of the NVU.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens / genetics
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Antigens / metabolism
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Astrocytes / cytology
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Astrocytes / metabolism
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Biomarkers / metabolism
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Blood-Brain Barrier / metabolism*
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Cell Differentiation
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Coculture Techniques
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Endothelial Cells / cytology
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Endothelial Cells / metabolism*
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Gene Expression
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Humans
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Induced Pluripotent Stem Cells / cytology
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Induced Pluripotent Stem Cells / metabolism*
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Male
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neural Crest / cytology
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Neural Crest / metabolism*
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Neurons / cytology
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Neurons / metabolism
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Pericytes / cytology
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Pericytes / metabolism*
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Primary Cell Culture
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Prosencephalon / cytology
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Prosencephalon / growth & development
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Prosencephalon / metabolism
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Proteoglycans / genetics
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Proteoglycans / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptor, Platelet-Derived Growth Factor beta / genetics
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Receptor, Platelet-Derived Growth Factor beta / metabolism
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Receptors, Nerve Growth Factor / genetics
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Receptors, Nerve Growth Factor / metabolism
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Transcytosis / genetics*
Substances
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Antigens
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Biomarkers
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NGFR protein, human
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Nerve Tissue Proteins
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Proteoglycans
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Receptors, Nerve Growth Factor
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chondroitin sulfate proteoglycan 4
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PDGFRB protein, human
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Receptor, Platelet-Derived Growth Factor beta