Lecocq, M. | bioRxiv Science

bioRxiv2026

RhythmWriter: GPU-accelerated Contractility Quantification for Large Datasets

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been considered optimal model systems for use in cardiac safety testing, yet their adoption remains low, largely because of technical limitations in the analysis methodology. RhythmWriter (RW) is an open-source GPU plugin for ImageJ developed to quantify contractile motion over extended periods of time. RW compensates for baseline drift, is time-scale invariant and is capable of very rapid data analysis. As a consequence, RW is capable of generating simultaneous high-resolution contraction restitution curves from multiple aggregates of hiPSC-CMs derived from premature-stimulus (S1S2) and dynamic-ramp restitution protocols. The aggregates exhibit brief refractory periods, which allow the induction of S2 beats at coupling intervals down to 130 ms and 1:1 entrainment during periodic stimulation down to a cycle length of 245 ms. Simulations confirm the ability of RW to track programmed contractile strength and stimulation intervals even at rapid pacing rates. This makes possible, for the first time, high-throughput functional assessment of hiPSC-CM aggregates for contractility drug screening and maturation.

physiology↗

bioRxiv2021

The memory of airway epithelium damage in smokers and COPD patients

RationaleChronic obstructive pulmonary disease (COPD) is a devastating and mostly irreversible lung disease. In COPD, the bronchial epithelium displays several structural and functional abnormalities affecting barrier integrity, cell polarity, and differentiation, as well as epithelial-to-mesenchymal transition and inflammation. Although COPD displays mostly irreversible changes, the (ir)reversible nature of epithelium pathology ex vivo remains poorly known and was the aim of this study. MethodsThe persistence of COPD epithelium abnormalities was addressed in long-term (10 weeks) primary cultures of air/liquid interface-reconstituted airway epithelium from non-smoker controls, smoker controls, and COPD patients. Barrier function, epithelial polarity, cell commitment, epithelial-to-mesenchymal transition and inflammation were assessed in vitro, and certain features were compared in situ to the native epithelium. The role of inflammation was explored by stimulating cultures with a cytokine mix consisting of TNF-, IL-6 and IL-1{beta}. Measurements and main resultsAlmost all epithelial defects (barrier dysfunction, impaired polarity, lineage abnormalities) observed in cells from smokers and COPD patients persisted in vitro up to week 10, except IL-8/CXCL-8 release and epithelial-to-mesenchymal transition which declined over time. Cell lineage and polarity impairments matched abnormalities observed in situ in the surgical samples from which the in vitro epithelium was derived. Cytokine treatment induced COPD-like changes and, in COPD cells, reactivated epithelial-to-mesenchymal transition. ConclusionsThe airway epithelium from smokers and COPD patients displays a memory of its native state and previous injuries by cigarette smoking, which is multidimensional and sustained for extended periods of time.

pathology↗