Mechanistic discoveries mostly rely on animal research or bioengineered human models. However, these platforms often fail to recapitulate human physiology and disease. Here we report a novel approach using adult human hearts, available from the UK NHS Blood and Transplant service, explanted exclusively for research and employed to prepare living myocardial slices (LMSs).
LMSs are ultrathin (300μm) sections of living cardiac tissue that can be prepared using a vibrating microtome from many species, including humans; LMSs maintain the native structure of the heart and can be kept in culture for weeks/months under physiological electro-mechanical conditions. We assessed whether preparing LMSs from donor human hearts is a viable and practical alternative to other research platforms.
From July 2024 to May 2025, we received 176 donor human heart offers. We accepted and used 31 hearts (15 of which donated after circulatory death, 16 donated after brain death), an almost ten-fold increase compared with previous years. The donors were 61 +/- 15.9 years of age (Mean +/- SD). We only accepted hearts from donors without cardiovascular disease or current infections and were within 6hrs transport time (transported in saline solution at 4oC). LMSs were prepared as described by our group previously (Camelliti et al., 2011; Pitoulis et al., 2020; van der Geest et al., 2025; Watson et al., 2019, 2017).
We could prepare 30-50 LMSs from a 1cm3 LV transmural biopsy. LMSs were viable and robust: (force transient amplitude at 2.2μm sarcomere length: 8.8 +/- 7.2mN/mm2; passive force: 9.4 +/- 6.6mN/mm2 (n=39)).
We also tested if it is possible to delay tissue utilisation, to facilitate high throughput, help with the arrival of tissue out-of-hours, and share it with other centres. There was no statistical difference in both force transient amplitude and passive force between fresh LMS and LMS from biopsies stored in cardioplegia for 5 hours at 4oC (active force fresh: 7.8 +/- 4.8mN/mm2; post-cardioplegia: 26.4+/-24mN/mm2; paired t-test: p=0.272; passive force fresh: 6.1+/-1.34mN/mm2; cardioplegia: 13.5+/-5.4mN/mm2; p=0.132, n=3 hearts from 8 fresh and 11 post-cardioplegia LMSs).
Adult donor heart tissue is a viable source of LMSs and can lead to valuable research in mechanisms of disease and treatment, as a valid alternative to animal research or bioengineered models.