Worldwide, there is growing belief that biomedical sciences can advance with less animal testing by replacing in-vivo experiments with in-vitro models based on human cells or tissues. However, when it comes to elucidating disease mechanisms, especially at the organ and system levels, or to testing the efficacy and safety of drugs and medical devices, animal models are as yet indispensable. This is why researchers – also at the Fraunhofer Institute for Toxicology and Experimental Medicine ITEM – are working to develop new human-relevant disease and test models according to the principle of the 3 Rs, both in vitro and ex vivo.