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Kasper Renggli
Scientist Systems Toxicology at PMI

Kasper Renggli received his B.Sc. in nanosciences from the University of Basel, Switzerland, finishing with a triple major in biology, chemistry and physics. During his Masters at the University of Basel, he spend an exchange semester at the Trinity College Dublin and completed his studies with a thesis on drug delivery using polymeric hybrid systems. In 2013, he defended his Ph.D. thesis in the Department of Chemistry of the University of Basel, working on protein engineering of nanoreactors for biotransformation and drug delivery. Subsequently, he received a Swiss National Science Foundation postdoctoral fellowship to join the DARPA human microphysiological organ systems program at the Massachusetts Institute of Technology (USA) to create a versatile microfluidic platform that can incorporate 10 individual engineered human microphysiological organ systems modules in an interacting circuit. There, he coached a team to engineer optimal conditions for the individual in vitro organ models with a focus on liver, gut and endometrium. From 2016 to 2019, he has been holding a group leader position at ETH Zürich, developing microphysiological systems to investigate tissue and disease models for personalized medicine approaches in close collaboration with leading hospitals in Switzerland. Furthermore, he worked with pharma on on pre-clinical development and pharmacology projects (oncology, immunology and safety). From 2017 to 2019 he completed the ECPM curriculum. In 2019, he joined Philip Morris International S.A. to help establish their capacity for systemic in vitro and in silico drug testing using novel tissue and disease models as well as microphysiological systems. He is an author of numerous publications and his work contributed to several patents.

OpenTox Virtual Conference 2023 

Session 9 - Organ on a Chip Innovation in Safer Design 

The limitations of animal models for modeling human disease and especially for predicting human responses to therapeutics are driving efforts to capture complex human physiology in culture with new biomaterials and devices that foster formation of 3D tissues and organ subsystems in vitro. Routinely, cell-based assessment in drug discovery is run on conventional 2-dimensional cell cultures grown in multi-well microtiter plates. Even though convenient to set up and carry out at high throughput, 2D monolayer structures often do not reflect their native 3-dimensional phenotype with respect to morphology and functionality. These limitations initiated many efforts in the last decades to develop 3D cell culture models that better reproduce the morphology and feature dynamic mechanical properties and biochemical functionalities of living organs. Furthermore, the design of microfluidic devices for cell cultures, especially multi-tissue cell cultures, has given rise to microfluidic designs for 2D and 3D cultures, which combine different cell types (tumor, liver, heart, lung etc.), fluidically interconnected in a physiologically relevant order. These microphysiological systems (MPS) are often considered the next step towards more comprehensive and representative in vitro testing systems. The interest in and relevance of these systems is mainly based on their potential to better predict the impact of compounds on processes in the human body and to better understand - in a more systemic way - how different organs interact with each other under different conditions. 

 HUMIMIC-InHALES: A Human-Relevant Aerosol Test Platform for Systemic Exposure Studies 

Current aerosol exposure systems suffer from the limitation that they expose only discrete parts of the human respiratory tract in static in vitro cultures to a fraction of a complex aerosol. This limits the predictive power of the generated data for respiratory and systemic human effects caused by such complex aerosols. 

Philip Morris International (PMI) developed the Independent Holistic Air–Air-Liquid Interface Exposure System (InHALES) as a mechanical replica of the whole human respiratory tract. It perfectly matches the architecture and respiratory characteristics of the human respiratory tract, including three relevant respiratory tract compartments [1]. PMI engineered InHALES to implement TissUse’s proprietary microphysiological HUMIMIC multi-organ-on-a-chip platform. A novel HUMIMIC chip for plug-and-play insertion into InHALES was developed to maintain and culture a human cell culture insert-based lung model with other organ equivalents (e.g., the liver). The use of new materials significantly reduced the absorption within the chip and allowed for testing of hydrophobic compounds. We have demonstrated the lung model’s integrity and viability using CellTrace™ Calcein Red-Orange AM and CellTox™ Green staining. The airway cultures in the HUMIMIC chip are subsequently exposed to physiological aerosols generated by the InHALES. 
With its combination of aerosol test system and cutting-edge microfluidics, HUMIMIC-InHALES supports the development of any systemic tests for aerosol exposure, including acute and chronic toxicity and long-term treatment efficacy. 

[1] S. Steiner et al., Toxicol In Vitro 2020, 67, 104909.