Hypoxia-enhanced Blood-Brain Barrier Chip recapitulates human barrier function and shuttling of drugs and antibodies
| Autor: | Anna Herland, Maximilian A. Benz, Olivier Y.F. Henry, Eric V. Shusta, Nur Mustafaoglu, Tae-Eun Park, Alexander L. Watters, Ryan M Hasselkus, Henry Sanchez, Edward A. FitzGerald, Sean P. Palecek, Robert Mannix, Hannah W. Song, Rachelle Prantil-Baun, Liliana Goumnerova, Heather J. McCrea, Donald E. Ingber |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Pluripotent Stem Cells
0301 basic medicine Endothelium Science Microfluidics Primary Cell Culture Drug Evaluation Preclinical General Physics and Astronomy Stem cells 02 engineering and technology Blood–brain barrier Article Antibodies Permeability General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Drug Delivery Systems In vivo Lab-On-A-Chip Devices medicine Humans Induced pluripotent stem cell lcsh:Science Barrier function Multidisciplinary Tight junction Drug discovery Chemistry Biological techniques Endothelial Cells General Chemistry Human brain 021001 nanoscience & nanotechnology Cell biology 030104 developmental biology medicine.anatomical_structure Transcytosis nervous system Blood-Brain Barrier Astrocytes Microvessels cardiovascular system lcsh:Q Endothelium Vascular Pericytes 0210 nano-technology Biotechnology Neuroscience |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-12 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | The high selectivity of the human blood-brain barrier (BBB) restricts delivery of many pharmaceuticals and therapeutic antibodies to the central nervous system. Here, we describe an in vitro microfluidic organ-on-a-chip BBB model lined by induced pluripotent stem cell-derived human brain microvascular endothelium interfaced with primary human brain astrocytes and pericytes that recapitulates the high level of barrier function of the in vivo human BBB for at least one week in culture. The endothelium expresses high levels of tight junction proteins and functional efflux pumps, and it displays selective transcytosis of peptides and antibodies previously observed in vivo. Increased barrier functionality was accomplished using a developmentally-inspired induction protocol that includes a period of differentiation under hypoxic conditions. This enhanced BBB Chip may therefore represent a new in vitro tool for development and validation of delivery systems that transport drugs and therapeutic antibodies across the human BBB. In vitro blood-brain barrier (BBB) models do not fully recapitulate the in vivo barrier function. Here the authors develop an organ-on-a-chip BBB model using iPS-derived human brain endothelial cells differentiated under hypoxia, primary human pericytes and astrocytes, which maintains in vivo-like BBB barrier and shuttling functions for a week. |
| Databáze: | OpenAIRE |
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