Modular Human Biochip-based Organoid Models in Biomedical Research
Animal models are frequently used in biomedical research. However, recently a controversial debate about the transferability of data obtained in mouse models to human conditions emerged. Although cell-based in vitro approaches can be an alternative, conventional cell culture methods hardly reflect cellular cross-communication and neglect essential physiological parameters of the living organism. We therefore develop biochip-embedded organoid models of the liver, gut and brain for use in basic medical research. The organoids are composed of essential human cell types of the respective organs and were tested in the context of sepsis-related organ dysfunction. Dynamic perfusion of biochip-embedded tissues allows an optimal supply with nutrients and oxygen, an efficient removal of catabolic metabolites, and enables a physiological cell polarization and communication within tissues. The modular approach of the biochip design allows a variable microfluidically interconnection of different organoid models in a freely selectable arrangement. Most important, the cellular processes observed under pathophysiological conditions in vitro closely resemble pathophysiological responses of established mouse models as well as clinical observations in human sepsis. Thus biochip-based organoid models are suitable experimental tools to improve study options on pathophysiological mechanisms of sepsis-related multi-organ failure and the development of targeted treatment strategies.