Growth of endothelial cells on microfabricated silicon nitride membranes for anin vitro model of the blood-brain barrier

Harris, Sarina; Shuler, Michael L.

doi:10.1007/bf02942273

Cited by 46 publications

(35 citation statements)

References 15 publications

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“…Although this channel has not been completely identified as a CNG channel, it was opened by an increase in the cAMP level (Figure 3), which subsequently allowed the inflow of Ca 2q ions. Protection of cells from apoptosis is also an important issue for cell-based biosensors on a chip (Harris and Shuler, 2003;Kim and Park, 2003). This heterologous expression system, which has cationic channels, represents a useful tool for addressing many curious unknown mechanisms of olfactory signal transduction and could also be used in cell-based olfactory biosensors.…”

Section: Discussionmentioning

confidence: 99%

Dual signal transduction mediated by a single type of olfactory receptor expressed in a heterologous system

Park

2006

Biological Chemistry

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Controversy exists over the relationship between the cAMP and IP3 pathways in vertebrate olfactory signal transduction, as this process is known to occur by either of the two pathways. Recent studies have shown that a single olfactory neuron responds to both cAMP- and IP3-producing odorants, suggesting the existence of an olfactory receptor protein that can recognize both ligands. In this study we found that the rat olfactory receptor I7, stably expressed in HEK-293 cells, triggers the cAMP pathway upon stimulation by a specific odorant (octanal) at concentrations lower than 10(-4) M; however, the receptor triggers both pathways at higher concentrations. This indicates that a single olfactory receptor, stimulated by a single pathway-inducing odorant, can evoke both pathways at high odorant concentrations. Using this heterologous system, both the dose-dependent response and receptor I7 specificity were analyzed. The dose-dependent Ca2+ response curve, which also includes the release of Ca2+ ions from internal stores at high odorant concentrations, was not monotonous, but had a local maximum and minimum with 10(-10) and 10(-7) M octanal, respectively, and reached a plateau at 10(-2) M octanal. The specificity of the I7 receptor was lower when exposed to higher concentrations of odorants.

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Section: Discussionmentioning

confidence: 99%

Dual signal transduction mediated by a single type of olfactory receptor expressed in a heterologous system

Park

2006

Biological Chemistry

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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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“…Commercially available membranes have a maximum porosity of 15%, are relatively thick (10 m), and only allow limited contact between the two cell types. Microfabricated membranes that are thinner and have a higher porosity such as those fabricated by Harris and Shuler (2003) might allow for a better contact between the cells.…”

Section: Challengesmentioning

confidence: 99%