Murine in vitro model of the blood–brain barrier for evaluating drug transport

Shayan, Gilda; Choi, Yong Seok; Shusta, Eric V.; Shuler, Michael L.; Lee, Kelvin H.

doi:10.1016/j.ejps.2010.11.005

Cited by 64 publications

(54 citation statements)

References 27 publications

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“…This way, a higher TEER and lower permeability was achieved compared to BMEC cultures alone, resembling more the in vivo situation (Shayan et al 2011). In addition, increased tight junction formation as well as increased expression of specific BBB markers, including transporters, was obtained (Cucullot et al 2006).…”

Section: Co-culturementioning

confidence: 92%

“…These two parameters are described in two different sections (''Permeability coefficient'' and ''The clearance''). Since the development of the first in vitro BBB model (Joo and Karnushi 1973), several co-culture systems were developed and further refined (Cecchelli et al 1999;Malina et al 2009;Shayan et al 2011). The brain endothelial cells were isolated from different species Walker and Coleman 1995).…”

Section: Surface Activitymentioning

confidence: 99%

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Brainpeps: the blood–brain barrier peptide database

et al. 2011

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Peptides are able to cross the blood-brain barrier (BBB) through various mechanisms, opening new diagnostic and therapeutic avenues. However, their BBB transport data are scattered in the literature over different disciplines, using different methodologies reporting different influx or efflux aspects. Therefore, a comprehensive BBB peptide database (Brainpeps) was constructed to collect the BBB data available in the literature. Brainpeps currently contains BBB transport information with positive as well as negative results. The database is a useful tool to prioritize peptide choices for evaluating different BBB responses or studying quantitative structure-property (BBB behaviour) relationships of peptides. Because a multitude of methods have been used to assess the BBB behaviour of compounds, we classified these methods and their responses. Moreover, the relationships between the different BBB transport methods have been clarified and visualized.

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Section: Co-culturementioning

confidence: 92%

Section: Surface Activitymentioning

confidence: 99%

Brainpeps: the blood–brain barrier peptide database

et al. 2011

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“…Ultra-thin nanofabricated membranes can address these shortcomings because they constitute a highly porous surface with controlled pore dimensions and can be less than 3 mm thick. [160][161][162] Different membranes have demonstrated endothelial and astrocyte biocompatibility, and can potentially be used in other devices as a substitute for commercial systems.…”

Section: Central Nervous System (Cns)/peripheral Nervous System (Pns)mentioning

confidence: 99%

‘Body-on-a-Chip’ Technology and Supporting Microfluidics

Smith¹,

Long²,

McAleer³

et al. 2014

Human-Based Systems for Translational Research

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In order to effectively streamline current drug development protocols, there is a need to generate high information content preclinical screens capable of generating data with a predictive power in relation to the activity of novel therapeutics in humans. Given the poor predictive power of animal models, and the lack of complexity and interconnectivity of standard in vitro culture methodologies, many investigators are now moving toward the development of physiologically and functionally accurate culture platforms composed of human cells to investigate cellular responses to drug compounds in high-throughput preclinical studies. The generation of complex, multi-organ in vitro platforms, built to recapitulate physiological dimensions, flow rates and shear stresses, is being investigated as the logical extension of this drive. Production and application of a biologically accurate multi-organ platform, or ‘body-on-a-chip’, would facilitate the correct modelling of the dynamic and interconnected state of living systems for high-throughput drug studies as well as basic and applied biomolecular research. This chapter will discuss current technologies aimed at producing ‘body-on-a-chip’ models, as well as highlighting recent advances and important challenges still to be met in the development of biomimetic single-organ systems for drug development purposes.

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“…These will enable the testing of hypotheses related to the need for physical contact between endothelial cells and astrocytes. Recent work by Lippmann and colleagues [33] and by Shayan and colleagues [34] has shown that brain endothelial cells respond to the presence of astrocytes in culture, acquiring substantial barrier properties, as indicated by high transendothelial electrical resistance measurements.…”

Section: Barrier Tissues Modelmentioning

confidence: 99%

Microphysiological systems and low-cost microfluidic platform with analytics

et al. 2013

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A multiorgan, functional, human in vitro assay system or 'Body-on-a-Chip' would be of tremendous benefit to the drug discovery and toxicology industries, as well as providing a more biologically accurate model for the study of disease as well as applied and basic biological research. Here, we describe the advances our team has made towards this goal, as well as the most pertinent issues facing further development of these systems. Description is given of individual organ models with appropriate cellular functionality, and our efforts to produce human iterations of each using primary and stem cell sources for eventual incorporation into this system. Advancement of the 'Body-on-a-Chip' field is predicated on the availability of abundant sources of human cells, capable of full differentiation and maturation to adult phenotypes, for which researchers are largely dependent on stem cells. Although this level of maturation is not yet achievable in all cell types, the work of our group highlights the high level of functionality that can be achieved using current technology, for a wide variety of cell types. As availability of functional human cell types for in vitro culture increases, the potential to produce a multiorgan in vitro system capable of accurately reproducing acute and chronic human responses to chemical and pathological challenge in real time will also increase.

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Murine in vitro model of the blood–brain barrier for evaluating drug transport

Cited by 64 publications

References 27 publications

Brainpeps: the blood–brain barrier peptide database

Brainpeps: the blood–brain barrier peptide database

‘Body-on-a-Chip’ Technology and Supporting Microfluidics

Microphysiological systems and low-cost microfluidic platform with analytics

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