In the past toxicologist have relied heavily on animal or human subjects to study the interplay between chemical movement, blood ﬂow, and organ health. However, toxicity testing in the 21st century requires a new system to meet the needs of the rapidly changing drug, chemical, cosmetic, tobacco, markets, and personal care industries.
Single organ acute toxicity testing provides only part of the chemical toxicity story in vitro. The Interaction between key organ systems (e.g. intestine-to-liver) is an essential component to understanding the pharmacokinetics/pharmacodynamics of test chemicals.
IONTOX has found through working with collaborators in the pharmaceutical, chemical, cosmetics, and tobacco industries that there is a need for a multiple organ test system, with a simulated blood system, not just a ﬂuidics system that provides mechanical shear forces. The system should be ﬂexible with regard to the experimental design needs of the client. The ability to study two, three or four organ systems should be possible. Finally, the system should allow the use of cell or tissue models that are well characterized so that the data obtained is easily understood.
Through extensive research efforts with scientists from ScitoVation (formerly The Hamner Institutes) to develop pharmacokinetic models and studies with industry collaborators including British American Tobacco. IONTOX has developed a meso-scale, human based, ﬂexible, Human Dynamic Multiple Organ Plate (HuDMOPTM) with simulated blood ﬂow that can be used for assessing systemic toxicity.
• Multiple organs to be studied together.
• An understanding of pharmacokinetics.
• Compound effects on cell or tissue health to be monitored.
• More accurate in vitro to in vivo extrapolation
HuDMOPTM uses, human tissues representative of speciﬁc organs cultured in a custom designed mesoscale plate. Each organ compartment consists of tissue, interstitial space, and intravascular space. Organs are connected by a simulated vascular system that allows small molecules to enter and leave via passive diffusion through a semi-permeable membrane. Variations in organ mass and vascular perfusion area are taken into account in this model. There is no net exchange of culture media. This means that each organ cell/tissue can be cultured under optimal conditions.