The 52nd Congress of EuroTox
Integrated human multi-organ culture plate for estimating systemic toxicity in vitro
James M. Mckim1, Heidi Baas1, Miyoung Yoon2, Harvey
Clewell2 , Melvin E. Andersen2
1. IonTox, LLC
The development of in vitro alternative methods for predicting systemic toxicity requires an integrated model. Multiple organs should be represented in a single culture plate and these should be in communication via a simulated vasculature system. Because each tissue type in culture can have different media for optimal growth, this cannot be achieved by simply transferring culture medium from one organ to the next. Blood contains water, electrolytes, proteins, glucose, lipids, and cellular products. These substances can move from blood to interstitial space to cells by diffusion, filtration, osmosis, and active transport. Blood pressure and osmotic pressure can drive the movement of molecules. Test chemicals also move from blood into cells by these same processes. Thus, the vasculature system functions as a semipermeable membrane. The movement of selected substances and the balance between extracellular fluid and intracellular fluid is an important concept when designing multi-organ culture systems. Therefore, in order for in vitro data from multiple organ cultures to be relevant for predicting human effects, the communication between organ compartments should mimic as closely as possible in vivo fluid dynamics. In this way it is possible to develop physiologically based pharmacokinetic models for the in vitro system. The work presented here describes the development of a multi-organ cell culture system that utilizes multiple human tissues combined with a fluidics system that incorporates a semi-permeable membrane in the organ compartments. This allows for analyte movement without volume change and with-minimal change to the culture medium of each organ.
J.M. McKim, H. M. Baas, Miyoung Yoon, Harvey Clewell, Melvin E. Andersen. Integrated Human Multi-Organ Culture Plate for Estimating Systemic Toxicity In Vitro. In: Toxicology Letters: Abstracts of the 52nd Congress of the European Societies of Toxicology (EUROTOX) Fibes Congress Center Seville, 258 (Supplement 2016), European Society of Toxicology, 2016. Abstract S14-4