As an illustration of the advantages of our 3D ProtoTissue™
System for 3D culturing we have developed a Liver ProtoTissue™.
Liver ProtoTissue™ is generated from immortal liver cell lines
grown in the ProtoTissue™ Bioreactor for 20 days by which time they
have differentiated into a functional 3D human liver-like
tissue.
The Liver ProtoTissue™ is stable over several months and has
many features which structurally and functionally resemble the
human liver including the ability to continuously recover after
being exposed to drugs associated with liver toxicity multiple
times over several weeks.
Liver ProtoTissue™ can be cultured reproducibly and has been
characterized by numerous biological studies.
- Has ultrastructurally features that resemble the liver
- Is functionally stable for several months in our 3D
ProtoTissue™ System once differentiated
- Shows no apoptotic 'background'
- Secretes protein in proportions similar to that found in
blood
- Responds in a physiological manner to physiological levels of
insulin and glucagon
- Can synthesize cholesterol. This can be inhibited by
lovastatin
- Can synthesize and secrete bile acids. This secretion can be
enhanced by Phenobarbital
- Is sensitive to the glucose concentration in the media
- Expresses several cytochrome P450s. Their expression can be
stimulated by phenolbarbital
- Metabolizes known drugs similarly as liver tissuein vivo
Liver ProtoTissue™ has ultrastructural features that resemble
liver e.g. microvillae on sinusoidal faces, smooth lateral faces,
tight junctions, glycogen granules and bile canaliculae
Drug
testing:
Liver ProtoTissue™ adds a new dimension to in vitro
drug testing, allowing long term and multiple dosing studies to be
carried out that are not possible with other systems.
Liver ProtoTissue™ has proven to be a reproducible tool for
study of human liver reactions to drugs from 2 hours exposure up to
months after first dosing providing more detailed and highly
relevant information about drug candidates potentially reducing the
time of lead selection and assisting in decision-making during
clinical studies.
Liver
Prototissue™ applications
include:
- Reproducible investigation of both acute and chronic toxicity
effects over weeks or months
- Drug metabolites (including rare ones only seen after multiple
dosing) can be collected for further analysis
- Level of inhibition of particular P450 cytochromes
- Drug-drug interaction studies
The advantage of Liver ProtoTissue™ being a functional 3D human
liver-like tissue represents a robust and versatile in
vitro alternative to complicated liver clamped studies in
vitro.
Examples of
liver functionality studies employing Liver ProtoTissue™
include:
- General liver physiological functionality after various
treatments incl. drug testing
- Production of bile acids
- Glucose uptake
- Glycogen storage
- Cholesterol synthesis
- Insulin sensitivity