Living Organ Slices

Our primary research focus is the advancement and refinement of the living myocardial slice (LMS) platform, a physiologically relevant model for studying cardiac function and disease. LMS are ultrathin (300 μm), highly viable sections of the left ventricular myocardium that preserve the heart’s native multicellular composition, structural integrity, and physiological properties. As an intermediate-complexity system, LMS provide a unique opportunity to study cardiac tissue in a controlled yet physiologically relevant environment.

This platform allows for precise modulation of myocardial tissue at a macroscopic level while maintaining native cellular interactions. By applying various experimental interventions – such as chemical and biological compounds, mechanical loading, or cryoinjury – researchers can investigate disease mechanisms and assess potential therapeutic strategies in a setting that closely mimics in vivo conditions.

In our projects LMS have been successfully derived from a wide range of small and large mammals, including mice, rats, pigs, and human tissue obtained from biopsies or explanted hearts. Notably, multiple slices can be generated from a single heart or biopsy, enabling parallel experiments and significantly reducing the number of animals required for research. This not only enhances experimental efficiency but also supports ethical research practices by minimizing animal use.

Beyond cardiac research, we extend our work to patient-derived organ slices from liver and lung tissue, aiming to develop novel anti-fibrotic therapies. These models provide a valuable platform for studying fibrosis progression and testing potential drug candidates in a physiologically relevant setting, ultimately contributing to more effective treatments for fibrotic diseases.

Compound-based Therapeutics

Using our advanced physiological disease models, we assess novel compounds for their potential as therapeutic treatments in hypertrophic cardiomyopathy, myocardial infarction, and pathological remodeling in heart failure. By replicating disease conditions in a controlled environment, we aim to identify and validate effective compounds that can improve cardiac function and intervene at early stages to prevent disease progression.

Key references:

Schmidt K, Fuchs M, Weber N, Werlein C, Schmitto JD, Ius F, Ruhparwar A, Bär C, Fiedler J, Thum T. (2024) Single-nucleus RNA sequencing identifies cell-type-specific effects of sodium-glucose co-transporter 2 inhibitors in human myocardial slices. Eur Heart J. 45(35):3292-3295. https://doi.org/10.1093/eurheartj/ehae472

Abbas N., Haas J.A., Xiao K., Fuchs M., Just A., Pich A., Perbellini F., Ius F., Ruhparwar A., Fiedler J., Weber N., Thum T. (2024) MiR-21 inhibition results in cardioprotective effects in human heart failure ex vivo. Eur Heart J. 45(22):2016-2018. https://doi.org/10.1093/eurheartj/ehae102

Waleczek FJG, Sansonetti M, Xiao K, Jung M, Mitzka S, Weber N, Dendorfer A, Perbellini F, Thum T. (2022) Chemical and mechanical activation of resident cardiac macrophages in the living myocardial slice ex vivo model. Basic Res Cardiol. 117(1):63. https://doi.org/10.1007/s00395-022-00971-2

Foinquinos A, Batkai S, Genschel C, Viereck J, Rump S, Gyongyosi M, Traxler D, Riesenhuber M, Spannbauer A, Lukovic D, Weber N, Zlabinger K, Hasimbegovic E, Winkler J, Fiedler J, Dangwal S, Fischer M, de la Roche J, Wojciechowski D, Kraft T, Garamvolgyi R, Neitzel S, Chatterjee S, Yin X, Bar C, Mayr M, Xiao K, Thum T. (2022) Preclinical development of a miR-132 inhibitor for heart failure treatment. Nature Communications 11(1):633. https://doi.org/10.1038/s41467-020-14349-2