Human Blood-Brain Barrier Endothelial Cells Derived from Pluripotent Stem Cells
| Autor: | Lippmann, Ethan S., Azarin, Samira M., Kay, Jennifer E., Nessler, Randy A., Wilson, Hannah K., Al-Ahmad, Abraham, Palecek, Sean P., Shusta, Eric V. |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Nature biotechnology |
| ISSN: | 1546-1696 1087-0156 |
| Popis: | The blood-brain barrier (BBB) plays an important role in brain health and is often compromised in disease. Moreover, as a result of its significant barrier properties, this endothelial interface restricts neurotherapeutic uptake. Thus, a renewable source of human BBB endothelium could prove enabling for brain research and pharmaceutical development. Herein, we demonstrate that endothelial cells generated from human pluripotent stem cells (hPSCs) can be specified to possess many BBB attributes, including well-organized tight junctions, expression of nutrient transporters, and polarized efflux transporter activity. Importantly, hPSC-derived BBB endothelial cells respond to astrocytic cues yielding impressive barrier properties as measured by transendothelial electrical resistance (1450±140 Ωxcm2) and molecular permeability that correlates well with in vivo brain uptake. In addition, specification of hPSC-derived BBB endothelial cells occurs in concert with neural cell co-differentiation via Wnt/β-catenin signaling, consistent with previous transgenic studies. This study represents the first example of organ-specific endothelial differentiation from hPSCs. |
| Databáze: | OpenAIRE |
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