Biomedical Engineering Reference
In-Depth Information
blockers and toxins. Responses indicating major pathological membrane
currents in cells have also been studied with a third group of compounds
that cause paroxysmal responses. For example, the gp120 protein of the AIDS
virus produces massive, unique paroxysmal discharges that may last as long as
2 min.
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3.10.2 Microscale Cell Culture Analogues
In order to reach a more metabolically accurate model of the complex
biological systems that constitute the human physiology, microscale cell culture
analogues (CCAs) are grown on the surface of patterned microelectrode
surfaces. Such in vitro human surrogates can contribute to a more profound
understanding of the biology of cells and, at the same time, lead to the
reduction, refinement or replacement (the '3Rs' principle) of animal testing in
the drug or cosmetic industries. Besides, to extrapolate animal data to humans
might just be irrelevant in many cases. The animal studies are not only
expensive and lengthy, but also raise essential ethical issues.
Instead of using a culture of a single type of cells, this approach counts in the
exchange of metabolites between tissues such as liver, lung, skin, kidney, etc.
situated in separate compartments interconnected by a recirculated medium
mimicking the blood flow. In each compartment the potential reaction or
adsorption kinetics of the chemical or its metabolites is estimated, potentially
predicting the time-dependent metabolism, excretion or adsorption of the
chemical and its metabolites. The CCA concept has been demonstrated in
simple macroscopic systems (e.g. liver-lung-other tissue) using naphthalene as
a model toxicant.
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Naphthalene is a representative of non-nutritive polycyclic
aromatic hydrocarbons (PAHs). In addition, a very simple human CCA model
for dioxin toxicity has been described.
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3.10.3 Microelectrode Arrays in Drug Discovery
Electrical activity of cells in neuronal tissue is always accompanied by the flow
of current through the extracellular fluid surrounding the cellular signal
sources. Related to the current is an extracellular voltage gradient that varies in
time and space according to the time course of the temporal activity and spatial
distribution and orientation of the cells. MEAs offer the unique possibility for
non-invasive, simultaneous recording of this activity of cells and networks.
Recording experiments using MEAs can mostly be considered as having the
following motivations:
I. To gain information about interactions between electrogenic cells at
different locations in the same tissue, which may be used to analyze the
spatio-temporal dynamics of activity or the representation of informa-
tion in neuronal networks;
II. To reduce the time required for an experiment by simultaneously
recording at several sites in parallel, and thus sample the distribution of
