CORESTA Meeting, Smoke Science/Product Technology, 2019, Hamburg, STW 04

Multi-organ-on-a-chip platforms to assess the biological impact of toxicants as well as PBPK properties in vitro

FRENTZEL S.; BOVARD D.; SANDOZ A.; LUETTICH K.; HOENG J.; PEITSCH M.C.
PMI R&D, Philip Morris Products S.A., Neuchâtel, Switzerland

The merging of three-dimensional (3D) organotypic in vitro models with multi-organ-on-a-chip (MOC) technology has taken in vitro assessment of chemicals to an unprecedented level. By connecting multiple 3D organotypic models, MOCs enable the study of organ cross-talk, thereby placing the evaluation of compound safety and efficacy much closer to human exposure conditions. In particular MOCs, utilizing human airway epithelial air-liquid interface (ALI) culture models, could advance the toxicological assessment of aerosols in vitro. In contrast to models kept in static culture conditions, the microfluidics connecting the organ models in MOCs mimic the dynamic conditions in the blood circulation. Therefore physiologically-based pharmacokinetic (PBPK) modelling, based on MOC data, can better simulate exposure-responses in vivo. Furthermore, the presence of metabolically active 3D organotypic liver spheroids in lung-liver MOCs can provide valuable information about biotransformation of aerosol constituents and their potential harm.

This presentation intends to provide a general overview of MOC platforms and their applicability to next generation tobacco and nicotine product assessment. Additionally, a MOC recently developed by us will be highlighted as an example for a lung-liver chip model where the metabolizing capacity of liver spheroids present in the chip can modulate the biological impact of a toxicant.