Development of a Microscale Cell Culture Analog To Probe Naphthalene Toxicity

Viravaidya, Kwanchanok; Sin, Aaron; Shuler, Michael L.

doi:10.1021/bp0341996

Cited by 285 publications

(249 citation statements)

References 32 publications

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“…Details of design and operation are given elsewhere. 17,22,25,28 The system has been used to determine response to naphthalene as a model toxicant. Naphthalene is not toxic itself, but activated in the liver to a reactive form, which causes cell death in other organs, such as the lung.…”

Section: Living Cell Models Of Humansmentioning

confidence: 99%

Modeling Life

Shuler

2012

Ann Biomed Eng

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Abstract-We seek to construct physical and mathematical models of life. Such models allow us to test our understanding of how living systems function and how they respond to human imposed stimuli. One system is a genomically and chemically complete model of a minimal cell. This cell is a hypothetical bacterium with the fewest number of genes possible. Such a minimal cell provides a platform to ask about the essential features of a living cell and forms a platform to investigate ''synthetic biology.'' A second system is ''Body-on-a-Chip'' which is a microfabricated microfluidic system with cells or tissue constructs representing various organs in the body. It can be constructed from human or animal cells and used in drug discovery development. That model is a physical representation of a physiologically based pharmacokinetic model. Both the computer and the physical models provide insight into the underlying biology and provide new tools to make use of that understanding to provide benefits to society.

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Section: Living Cell Models Of Humansmentioning

confidence: 99%

Modeling Life

Shuler

2012

Ann Biomed Eng

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“…28 A chip with few channels and chambers each housing a different cell type was constructed to mimic the functions of a multiorgan organism. 183 This CCA ͑microcell culture analog device͒ pioneered by Shuler's group is based on the structure of an appropriate physiologically based pharmacokinetic ͑PBPK͒ model and emulates the body's dynamic response to exposure to various drugs and chemicals. CCA was designed based on parameters such as: the ratio of the chamber sizes, the liquid residence times in each compartment, the minimum number of cells to facilitate analysis of chemicals, and the hydrodynamic shear stress on the cells complying with physiological values.…”

Section: A Drug Researchmentioning

confidence: 99%

Exploitation of physical and chemical constraints for three-dimensional microtissue construction in microfluidics

Choudhury

Iliescu

et al. 2011

Biomicrofluidics

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There are a plethora of approaches to construct microtissues as building blocks for the repair and regeneration of larger and complex tissues. Here we focus on various physical and chemical trapping methods for engineering three-dimensional microtissue constructs in microfluidic systems that recapitulate the in vivo tissue microstructures and functions. Advances in these in vitro tissue models have enabled various applications, including drug screening, disease or injury models, and cellbased biosensors. The future would see strides toward the mesoscale control of even finer tissue microstructures and the scaling of various designs for high throughput applications. These tools and knowledge will establish the foundation for precision engineering of complex tissues of the internal organs for biomedical applications.

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“…This allows study of mechanisms that may not be anticipated or predicted from mathematical models. CCAs can be fabricated to incorporate several separate compartments corresponding to various organs including lung, liver, and adipose tissue [169]. Each compartment is connected to the next by fluidics, providing a continuous flow of medium for perfusion of the cell system, which is usually contained within a hydrogel matrix.…”

Section: Cell Culture Analog Systemsmentioning

confidence: 99%

“…In one example, bioconversion of naphthalene and GST activity were measured in real time [169]. Blood-brain barrier models may eventually be incorporated into these multi-compartment CCA systems or other bioreactor systems, for assessment of the bioconversion and permeability of neuroactive compounds.…”

Section: Cell Culture Analog Systemsmentioning

confidence: 99%

Biomedical Technologies for In Vitro Screening and Controlled Delivery of Neuroactive Compounds

Frampton¹,

Shuler²,

Shain³

et al. 2008

CNSAMC

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Cell culture models can provide information pertaining to the effective dose, toxiciology, and kinetics, for a variety of neuroactive compounds. However, many in vitro models fail to adequately predict how such compounds will perform in a living organism. At the systems level, interactions between organs can dramatically affect the properties of a compound by alteration of its biological activity or by elimination of it from the body. At the tissue level, interaction between cell types can alter the transport properties of a particular compound, or can buffer its effects on target cells by uptake, processing, or changes in chemical signaling between cells. In any given tissue, cells exist in a three-dimensional environment bounded on all sides by other cells and components of the extracellular matrix, providing kinetics that are dramatically different from the kinetics in traditional two-dimensional cell culture systems. Cell culture analogs are currently being developed to better model the complex transport and processing that occur prior to drug uptake in the CNS, and to predict blood-brain barrier permeability. These approaches utilize microfluidics, hydrogel matrices, and a variety of cell types (including lung epithelial cells, hepatocytes, adipocytes, glial cells, and neurons) to more accurately model drug transport and biological activity. Similar strategies are also being used to control both the spatial and temporal release of therapeutic compounds for targeted treatment of CNS disease.

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Development of a Microscale Cell Culture Analog To Probe Naphthalene Toxicity

Cited by 285 publications

References 32 publications

Modeling Life

Modeling Life

Exploitation of physical and chemical constraints for three-dimensional microtissue construction in microfluidics

Biomedical Technologies for In Vitro Screening and Controlled Delivery of Neuroactive Compounds

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