TY - JOUR
T1 - Animal models and animal-free innovations for cardiovascular research
T2 - 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
AU - van der Velden, Jolanda
AU - Asselbergs, Folkert W.
AU - Bakkers, Jeroen
AU - Batkai, Sandor
AU - Bertrand, Luc
AU - Bezzina, Connie R.
AU - Bot, Ilze
AU - Brundel, Bianca J.J.M.
AU - Carrier, Lucie
AU - Chamuleau, Steven
AU - Ciccarelli, Michele
AU - Dawson, Dana
AU - Davidson, Sean M.
AU - Dendorfer, Andreas
AU - Duncker, Dirk J.
AU - Eschenhagen, Thomas
AU - Fabritz, Larissa
AU - Falcão-Pires, Ines
AU - Ferdinandy, Péter
AU - Giacca, Mauro
AU - Girao, Henrique
AU - Gollmann-Tepeköylü, Can
AU - Gyongyosi, Mariann
AU - Guzik, Tomasz J.
AU - Hamdani, Nazha
AU - Heymans, Stephane
AU - Hilfiker, Andres
AU - Hilfiker-Kleiner, Denise
AU - Hoekstra, Alfons G.
AU - Hulot, Jean Sébastien
AU - Kuster, Diederik W.D.
AU - van Laake, Linda W.
AU - Lecour, Sandrine
AU - Leiner, Tim
AU - Linke, Wolfgang A.
AU - Lumens, Joost
AU - Lutgens, Esther
AU - Madonna, Rosalinda
AU - Maegdefessel, Lars
AU - Mayr, Manuel
AU - van der Meer, Peter
AU - Passier, Robert
AU - Perbellini, Filippo
AU - Perrino, Cinzia
AU - Pesce, Maurizio
AU - Priori, Silvia
AU - Remme, Carol Ann
AU - Rosenhahn, Bodo
AU - Schotten, Ulrich
AU - Schulz, Rainer
AU - Sipido, Karin R.
AU - Sluijter, Joost P.G.
AU - van Steenbeek, Frank
AU - Steffens, Sabine
AU - Terracciano, Cesare M.
AU - Tocchetti, Carlo Gabriele
AU - Vlasman, Patricia
AU - Yeung, Kak Khee
AU - Zacchigna, Serena
AU - Zwaagman, Dayenne
AU - Thum, Thomas
N1 - Publisher Copyright: © The Author(s) 2022.
PY - 2022/11
Y1 - 2022/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85126467892&partnerID=8YFLogxK
U2 - 10.1093/cvr/cvab370
DO - 10.1093/cvr/cvab370
M3 - Review article
C2 - 34999816
AN - SCOPUS:85126467892
SN - 0008-6363
VL - 118
SP - 3016
EP - 3051
JO - Cardiovascular Research
JF - Cardiovascular Research
IS - 15
ER -