{
  "abstract": "Introduction Atrial fibrillation (AF) is the most common cause of cardiac arrhythmia globally, highlighting the need for an effective in vitro model to study cardiac physiology and contractility. Investigating human atrial cardiomyocytes in three-dimensional structures will enhance our understanding of their role in atrial physiology and open avenues to explore cell-cell interactions compared to two-dimensional cultures. In this study, we have engineered three-dimensional myocardial microtissues which could offer significant advantages in modelling atrial physiology in vitro and investigating cardiac contractile function and electrophysiology.Methods Human induced pluripotent stem cells (iPSCs) were differentiated into ventricular and atrial cardiomyocytes, which were then seeded into non-adherent microwells to form spheroids and into 48 well plates to form monolayers. Spontaneous contractility recordings were performed daily from the onset of cardiomyocyte beating, assessing contraction amplitude, time to peak contraction, and relaxation time. Additionally, calcium transients were recorded to evaluate calcium handling dynamics.Results Contractility analysis shows that atrial spheroids have significantly shorter contraction duration in comparison to atrial monolayers (259 ± 27 vs. 474 ± 31 ms; p=0.0012, n=4/8), and higher contraction amplitude (444 ± 25 vs. 153 ± 17 a.u.; p<0.0001, n=4/8). Atrial spheroids display a higher spontaneous beating frequency compared to ventricular spheroids (2 ± 0.2497 vs. 0.4 ± 0.0367 Hz; p=0.0037, n=7) and shorter contraction duration after correction for inter-beat interval (289 ± 9 vs. 365 ± 7 ms; p=0.0015, n=4/3). Calcium imaging at 1.5 Hz stimulation reveals chamber-specific differences, with atrial spheroids showing significantly shorter time to calcium peak (67 ± 5 vs. 143 ± 6 ms; p<0.0001, n=5) and shorter calcium transient duration (289 ± 21 vs. 396 ± 11 ms; p=0.0018, n=5).Conclusion Our results reveal distinct electrophysiological and contractile differences between atrial cardiomyocytes cultured in 3D spheroids and 2D monolayers, highlighting the influence of in vitro culture conditions on cellular behaviour. Atrial spheroids provide a more physiologically relevant platform, with an atrial-specific phenotype, offering promising applications for studying cell-cell interactions and their role in AF pathogenesis.",
  "authors": [
    {
      "affiliations": [
        "School of Biosciences, University of Surrey, Guildford, UK"
      ],
      "name": "Millie Trowbridge"
    },
    {
      "affiliations": [
        "School of Biosciences, University of Surrey, Guildford, UK"
      ],
      "name": "Rahul Sanwlani"
    },
    {
      "affiliations": [
        "School of Biosciences, University of Surrey, Guildford, UK"
      ],
      "name": "Rachel Simmonds"
    },
    {
      "affiliations": [
        "School of Biosciences, University of Surrey, Guildford, UK"
      ],
      "name": "Patrizia Camelliti"
    }
  ],
  "title": "BS49 3D human IPSC-derived atrial spheroids as a novel platform to study atrial electrophysiology",
  "uid": "2a0d19cb-c363-55c3-a115-115a0a434334"
}