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

authored by

Jolanda van der Velden, Folkert W. Asselbergs, Jeroen Bakkers, Sandor Batkai, Luc Bertrand, Connie R. Bezzina, Ilze Bot, Bianca J.J.M. 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 Giacca, Henrique 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 R. 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

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.

Organisation(s)

Institute of Information Processing

External Organisation(s)

Vrije Universiteit
Interuniversity Cardiology Institute of the Netherlands
Utrecht University
University College London (UCL)
Hannover Medical School (MHH)
Université catholique de Louvain (UCL)
University of Amsterdam
Leiden Academic Centre for Drug Research
Universität Hamburg
German Centre for Cardiovascular Research
Universita di Salerno
University of Aberdeen
Ludwig-Maximilians-Universität München (LMU)
Erasmus University Rotterdam
University Medical Center Hamburg-Eppendorf
University of Birmingham
Universidade do Porto
Semmelweis University
Pharmahungary Group
University of Trieste
International Centre for Genetic Engineering and Biotechnology
King's College London
Clinical Academic Centre of Coimbra (CACC)
Innsbruck Medical University
Medical University of Vienna
University of Glasgow
Ruhr-Universität Bochum
Maastricht University
KU Leuven
Philipps-Universität Marburg
Paris-Centre de Recherche Cardiovasculaire (PARCC)
Hopital Europeen Georges-Pompidou
University of Cape Town (UCT)
University of Münster
University of Pisa
University of Texas Health Science Center at Houston
Technical University of Munich (TUM)
Karolinska Institutet
University of Groningen
University of Twente
Leiden University
Monte S. Angelo University Federico II
IRCCS Centro Cardiologico Monzino
Istituti Clinici Scientifici Maugeri
University of Pavia
Justus Liebig University Giessen
Imperial College London
Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM)
Amsterdam UMC - Unversity Medical Centers
Jagiellonian University (UJ)

Type

Review article

Journal

Cardiovascular research

Volume

118

Pages

3016-3051

No. of pages

36

ISSN

0008-6363

Publication date

11.2022

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

General Medicine

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.1093/cvr/cvab370 (Access: Open)