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

Jolanda van der Velden, Folkert W Asselbergs, Jeroen Bakkers, Sandor Batkai, Luc Bertrand, Connie R Bezzina, Ilze Bot, Bianca Brundel, Lucie Carrier, Steven Chamuleau, Michele Ciccarelli, Dana Dawson, Sean M Davidson, Andreas Dendorfer, Dirk J Duncker, Thomas Eschenhagen, Larissa Fabritz, Ines Falcão-Pires, Péter Ferdinandy, Mauro GiaccaHenrique Girao, Can Gollmann-Tepeköylü, Mariann Gyongyosi, Tomasz J Guzik, Nazha Hamdani, Stephane Heymans, Andres Hilfiker, Denise Hilfiker-Kleiner, Alfons G Hoekstra, Jean-Sébastien Hulot, Diederik W D Kuster, Linda W van Laake, Sandrine Lecour, Tim Leiner, Wolfgang A Linke, Joost Lumens, Esther Lutgens, Rosalinda Madonna, Lars Maegdefessel, Manuel Mayr, Peter van der Meer, Robert Passier, Filippo Perbellini, Cinzia Perrino, Maurizio Pesce, Silvia Priori, Carol Ann Remme, Bodo Rosenhahn, Ulrich Schotten, Rainer Schulz, Karin Sipido, Joost P G Sluijter, Frank van Steenbeek, Sabine Steffens, Cesare M Terracciano, Carlo Gabriele Tocchetti, Patricia Vlasman, Kak Khee Yeung, Serena Zacchigna, Dayenne Zwaagman, Thomas Thum

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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 co-morbidities. 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 cannot provide a vital step in the translational pathway as they do provide important pathophysiological insights into disease mechanisms particularly on a 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 improved current 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. [Abstract copyright: Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions please email: journals.permissions@oup.com.]
Original languageEnglish
JournalCardiovascular Research
Early online date6 Jan 2022
DOIs
Publication statusE-pub ahead of print - 6 Jan 2022

Keywords

  • cardiovascular disease
  • co-morbidities
  • network medicine
  • big data
  • multiomics
  • bioinformatics
  • tissue engineering
  • iPSC

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