BS57 Safety and feasibility of isolating human cardiomyocytes from small cardiac tissue biopsies from elective surgical patients: a potential platform for human cardiac models

Background While animal cell models are pivotal for studying cardiac disease, their disparity from human myocardium necessitates a more physiologically relevant human model. Current studies with human cardiomyocytes often rely on large cardiac specimens from whole hearts, that are rapidly transported between the surgical theatre and adjacent research lab— resources that are not universally available across research institutions. Our study aims to address this gap by using significantly smaller cardiac tissue samples from elective surgical patients to isolate human myocytes, with longer transport times to the research lab. If successful, this approach could benefit the wider research community in studying human cardiomyocyte structure, contractility, electrophysiology, and drug cardiotoxicity across a wide spectrum of cardiac diseases. Methods In this single-centre study (ethical approval REC: 21/WA/0138), left ventricular and right atrial appendage tissue biopsies were obtained from consented patients undergoing coronary artery bypass grafting (CABG) and/or valve replacement. A 14G Tru-cut needle was used for ventricular biopsies (figure 1A). Specimens were transported at 4'C to the research lab approximately 4 miles from the surgical theatre. Optimisation of cell yield was achieved by testing various concentrations and combinations of enzymes and buffer compositions. Cell viability was assessed by the presence of rod-shaped myocytes with intact cell edges, clear striations and absence of spontaneous contractions. Sarcomeric length was measured optically by fast Fourier transformation (IonWizard, IonOptix). Results Myocardial tissue samples were obtained from 66 elective surgical patients, with a mean age of 68.1±8.3. Among them, 56% underwent isolated CABG and 44% aortic valve replacement. Average left ventricular ejection fraction (LVEF) was 51.2±10.4% (range 20–65%). Notably, no patients experienced complications from the research biopsy procedure. In contrast to previous studies utilising large cardiac tissue chunks up to 2–3 grams, the dry weight of myocardial tissue in our study averaged 0.105±0.069 grams (figure 1B). Mean transport time was 29.7±4.7 minutes. Despite these challenges, we were able to isolate human myocytes with measurable sarcomeric length on contraction (figure 1C). The average cell yield was 6.8% with significant variability ranging from 0 to 40%, depending on a multitude of experimental factors and tissue quality. In patients with LVEFConclusion This proof-of-concept study demonstrates the feasibility and safety of isolating human myocytes from small cardiac tissue biopsies, regardless of the degree of LVEF and transport time. Henceforth, further refinement of the experimental conditions will be necessary to achieve a consistently high cell yield of robust calcium-tolerant myocytes for subsequent force-length contractility and electrophysiology studies in a range of cardiac diseases. Conflict of Interest None