In the reporting period,
a protocol has been developed for quantitative observation of metabolic consumption/production
rates of live
mouse liver tissue. The method has been used to compare the impact of
drug-induced cholestasis, a common and troublesome side effect of many drugs,
on tissue metabolism. The results have been correlated with a comprehensive
study of bile transporter expression under the same conditions.
The NMR probe technology that allows integration of microfluidic perfusion
systems with high-resolution nuclear magnetic resonance (NMR) spectroscopy
represents a significant step beyond the existing state of the art.
To date, only very simple microfluidic NMR systems have been demonstrated.
While these have been limited to a capillary through which the microfluidic sample must be
pumped, the new designs developed and proved as part of TISuMR can
accommodate arbitrarily complex mircofluidic systems. This has deep implications
in that it provides the emerging field of microfluidic lab-on-a-chip systems
with a new modality of observation, which is largely orthogonal to the existing
ones: NMR is non-invasive, gives system-wide information on the metabolic
activitives of live systems, and is an inherently quantitative technique.
The characterisation of cholestasis on the level of liver tissue is also an
important step forward. Many important drugs are limited in their use by
cholestatic side effects, and drug-induced cholestasis leads to the eliminiation
of a large number of otherwise promising new drug candidates.
On the whole, the TISuMR project has turned what was at best a "future" technology
into a very much emerging one.
The result is a new technological platform for the culture and detailed metabolic observation of
live tissue samples, with important implications across the life sciences.
