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

verfasst von

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.

Organisationseinheit(en)

Institut für Informationsverarbeitung

Externe Organisation(en)

Vrije Universiteit Amsterdam
Interuniversity Cardiology Institute of the Netherlands
Utrecht University
University College London (UCL)
Medizinische Hochschule Hannover (MHH)
Katholische Universität Löwen (UCL)
Universiteit van Amsterdam (UvA)
Leiden Academic Centre for Drug Research (LACDR)
Universität Hamburg
Deutsches Zentrum für Herz-Kreislauf-Forschung eV
Universita di Salerno
University of Aberdeen
Ludwig-Maximilians-Universität München (LMU)
Erasmus University Rotterdam
Universitätsklinikum 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
Medizinische Universität Wien
University of Glasgow
Ruhr-Universität Bochum
Maastricht University
KU Leuven
Philipps-Universität Marburg
Paris-Centre de Recherche Cardiovasculaire (PARCC)
Hopital Europeen Georges-Pompidou
Universität Kapstadt (UCT)
Westfälische Wilhelms-Universität Münster (WWU)
University of Pisa
University of Texas Health Science Center at Houston
Technische Universität München (TUM)
Karolinska Institutet
Reichsuniversität Groningen
University of Twente
Leiden University
Università degli Studi di Napoli Federico II
IRCCS Centro Cardiologico Monzino
Istituti Clinici Scientifici Maugeri
Università degli Studi di Pavia
Justus-Liebig-Universität Gießen
Imperial College London
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin (ITEM)
Amsterdam UMC - Unversity Medical Centers
Uniwersytet Jagielloński (UJ)

Typ

Übersichtsarbeit

Journal

Cardiovascular research

Band

118

Seiten

3016-3051

Anzahl der Seiten

36

ISSN

0008-6363

Publikationsdatum

11.2022

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Allgemeine Medizin

Ziele für nachhaltige Entwicklung

SDG 3 – Gute Gesundheit und Wohlergehen

Elektronische Version(en)

https://doi.org/10.1093/cvr/cvab370 (Zugang: Offen)