Animal models and animal-free innovations for cardiovascular research: current status and routes to be explored. Consensus document of the ESC Working Group on Myocardial Function and the ESC Working Group on Cellular Biology of the Heart
Authors: van der Velden Jolanda , Asselbergs Folkert W , Bakkers Jeroen , Batkai Sandor , Bertrand Luc , Bezzina Connie R , Bot Ilze , Brundel Bianca J J M , Carrier Lucie , Chamuleau Steven , Ciccarelli Michele , Dawson Dana , Davidson Sean M , Dendorfer Andreas , Duncker Dirk J , Eschenhagen Thomas , Fabritz Larissa , Falcão-Pires Ines , Ferdinandy Péter , Giacca Mauro , Girao Henrique , Gollmann-Tepeköylü Can , Gyongyosi Mariann , Guzik Tomasz J , Hamdani Nazha , Heymans Stephane , Hilfiker Andres , Hilfiker-Kleiner Denise , Hoekstra Alfons G , Hulot Jean-Sébastien , Kuster Diederik W D , van Laake Linda W , Lecour Sandrine , Leiner Tim , Linke Wolfgang A , Lumens Joost , Lutgens Esther , Madonna Rosalinda , Maegdefessel Lars , Mayr Manuel , van der Meer Peter , Passier Robert , Perbellini Filippo , Perrino Cinzia , Pesce Maurizio , Priori Silvia , Remme Carol Ann , Rosenhahn Bodo , Schotten Ulrich , Schulz Rainer , Sipido Karin R , Sluijter Joost P G , van Steenbeek Frank , Steffens Sabine , Terracciano Cesare M , Tocchetti Carlo Gabriele , Vlasman Patricia , Yeung Kak Khee , Zacchigna Serena , Zwaagman Dayenne , Thum Thomas 
Published: January 2022

Abstract
Cardiovascular diseases represent a major cause of morbidity and mortality, necessitating research to improve diagnostics, and to discover and test novel preventive and curative therapies, all of which warrant experimental models that recapitulate human disease. The translation of basic science results to clinical practice is a challenging task, in particular for complex conditions such as cardiovascular diseases, which often result from multiple risk factors and comorbidities. This difficulty might lead some individuals to question the value of animal research, citing the translational ‘valley of death’, which largely reflects the fact that studies in rodents are difficult to translate to humans. This is also influenced by the fact that new, human-derived in vitro models can recapitulate aspects of disease processes. However, it would be a mistake to think that animal models do not represent a vital step in the translational pathway as they do provide important pathophysiological insights into disease mechanisms particularly on an organ and systemic level. While stem cell-derived human models have the potential to become key in testing toxicity and effectiveness of new drugs, we need to be realistic, and carefully validate all new human-like disease models. In this position paper, we highlight recent advances in trying to reduce the number of animals for cardiovascular research ranging from stem cell-derived models to in situ modelling of heart properties, bioinformatic models based on large datasets, and state-of-the-art animal models, which show clinically relevant characteristics observed in patients with a cardiovascular disease. We aim to provide a guide to help researchers in their experimental design to translate bench findings to clinical routine taking the replacement, reduction, and refinement (3R) as a guiding concept.