Scientists at the University Medical Center and the University of Göttingen have developed a new approach to keep intact heart tissue for about two weeks in culture for more efficient cardiotoxicity screening of new active substances and therapeutic approaches. The advantage: this method is already effective in a very early test phase, even before preclinical screening in the living organism. The results were published in the renowned journal Cardiovascular Research.
Newly developed drugs and therapeutic approaches often have side effects on the heart. Com-prehensive preclinical testing of new drug candidates therefore precedes clinical trials and appli-cation, with the aim of ruling out potential side effects as far as possible in advance. However, current procedures usually only cover part of the possible side effects on the heart. Improving the test procedures is therefore essential in order to predict the risk of undesirable side effects with a high degree of specificity and sensitivity.
A team led by Prof. Dr. Tobias Brügmann, research group leader at the Institute of Cardiovascu-lar Physiology at the University Medical Center Göttingen (UMG) in cooperation with Prof. Dr. Tim Salditt, Director of the Institute of X-ray Physics at the University of Göttingen, both members of the Cluster of Excellence “Multiscale Bioimaging: From Molecular Machines to Networks of Excit-able Cells” (MBExC), have now developed a way to keep fresh slices of intact heart tissue in cul-ture for up to two weeks. The vitality and functionality of the cardiomyocytes was demonstrably preserved, which was previously only possible for a few hours. This enables to more efficiently screen and detect the effects of new potential drugs on the electrical and contractile properties of cardiomyocytes and on the general tissue architecture over a longer time period before the active substances are used for analyses in living organisms.
Shi R, Reichardt M, Fiegle DJ, Küpfer LK, Czajka T, Sun Z, Salditt T, Dendorfer A, Seidel T, Bruegmann T (2023) Contractility measurements for cardiotoxicity screening with ventricular myocardial slices of pigs. Cardiovascular Research, Volume 119, Issue 14, October 2023, Pages 2469–2481. DOI: 10.1093/cvr/cvad141
About the method
The scientists first prepare thin (300 µm) tissue slices from pig hearts. Pig hearts are very similar to human hearts, from which there are hardly any opportunities to obtain samples for drug studies. Using a newly developed approach of cultivation, the scientists succeeded for the first time in keeping the tissue slices, which consist of intact heart muscle tissue, for up to two weeks in an incubator. As the scientists demonstrated, not only the typical shape of the heart muscle cells is preserved over the entire period, but also their vitality and functionality. So far, this was only possible for a couple of hours but is an absolute prerequisite in order to comprehensively ana-lyze the effects of various substances, such as new potential drugs or therapeutic approaches. The general suitability of the test procedure was first tested with drugs with known and well de-scribed effects on the heart. The scientists then tested in blinded trials whether they could relia-bly identify those substances with side effects on the heart among several, which was successful in every respect. “Identifying undesirable side effects on the heart as early and efficiently as possible is crucial to lower the health risk for patients in clinical trials later on. Moreover, this will also help to reduce the costs of drug development,” explains Prof. Dr. Brügmann. We are now in a position to test potential new drugs and new therapeutic approaches much more comprehen-sively in advance concerning their suitability for later use in clinical trials,” says Brügmann.
About Brügmann Lab: https://hkp.umg.eu/en/research/vegetative-optogenetics/
University Medical Center Göttingen, University of Göttingen
Institute of Cardiovascular Physiology Head of the Vegetative Optogenetics working group
Prof. Dr. Tobias Brügmann Phone +49 551 / 39-65526
Multiscale Bioimaging Cluster of Excellence (MBExC)
Dr. Heike Conrad (press contact)
Phone +49 551 / 39-61305
Link to the Press release (in German)
Link to the Pdf of the press release: