Exploring Multi‐Organ Crosstalk via the TissUse HUMIMIC Chip System: Lessons Learnt So Far

Three-dimensional (3D) in vitro cell culture models have revolutionized biomedical research by mimicking the complex 3D in vivo environment in the human body. Different types of 3D models have been established, including heterotypic systems such as, organ-on-a-chips which have been further developed into multiorgan-on-chip systems that simulate or mimic the mutual and multiplex physiological communication between (distant) organs that may not be physically connected with each other known as multiorgan crosstalk/interactions. These multiorgan interactions have been shown to be mediated by various factors including cells, soluble mediators (growth factors, cytokines etc.,) and cellular vesicles and are responsible for regulating metabolic, inflammatory, and tissue repair processes in the body. Different multiorgan-on-chip systems have been developed to mimic and study these interactions and their role in various molecular and toxicological processes. Of these, the TissUse HUMIMIC Starter and Chip microphysiological system is a commercially available multiorgan model that has been used to study inter-organ crosstalk between organs such as the gut and liver, liver and brain, liver and kidney, among others and applied in cellular, molecular and toxicology studies to among other things aid in the reduction of animals in drug and toxicological research. In this review, we provide a brief overview of multiorgan systems and summarize studies that have specifically used the TissUse system to investigate multiorgan crosstalk in the human body to deliver an update in the field of multiorgan microphysiological systems.