Ischemic heart disease remains the leading cause of death worldwide. Yet studying the cellular events that occur during a heart attack has long been limited by the shortcomings of traditional animal models. In his doctoral dissertation, MSc Mahmoud Gaballa addressed this challenge by creating a microengineered “heart-on-a-chip” system built from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). This platform allowed him to simulate reduced oxygen supply—one of the defining features of a heart attack—and observe how human heart cells respond in real time.
Gaballa demonstrated that hypoxia rapidly disrupts the structure and function of cardiomyocytes, causing disorganized contractile filaments, impaired calcium handling, and an increased risk of dangerous arrhythmia.
“By combining stem-cell technology with organ-on-a-chip engineering, we can recreate the earliest moments of a heart attack directly in human cells. This not only deepens our scientific understanding of ischemic injury but also brings us closer to identifying more effective and clinically relevant therapies”, says Gaballa.
A major focus of the dissertation was evaluating levosimendan, a clinically used inotrope, and its active metabolite OR-1896. Both compounds significantly reduced hypoxia-induced arrhythmias, preserved cellular structure, stabilized calcium cycling, and improved mitochondrial function. The findings reveal that OR-1896 provides cardioprotection comparable to the parent drug. These results suggest that these compounds may have broader applications in protecting the heart during ischemic episodes.
A step toward more personalized cardiac care
In addition to modelling cardiac injury, Gaballa addressed a key limitation in stem-cell–derived cardiomyocytes: their immature and fetal-like phenotype. By culturing the cells in a fatty acid-based medium—closely mimicking the adult heart’s natural energy source—he achieved markedly improved cellular maturation. The treated cells showed more organized contractile structures, increased mitochondrial content, enhanced oxidative metabolism, and more adult-like structural, metabolic and mechanical performance. This advance is highly relevant for drug testing and personalized medicine, as it brings laboratory-grown heart cells closer to the physiological behavior of the human heart.
Overall, the findings offer a comprehensive and integrative framework for modelling ischemic injury, evaluating cardioprotective drugs, and improving the maturity of hiPSC-CMs.
“Our goal is to develop platforms that better predict how human hearts respond to disease and treatment. Such models can accelerate drug discovery, reduce reliance on animal testing, and ultimately guide more personalized approaches to cardiac care”, Gaballa explains.
Gaballa’s work contributes both to fundamental understanding of ischemic heart disease and to the development of next-generation human heart models for research, pharmaceutical screening, and future individualized therapies.
Gaballa, originally from Egypt, is currently conducting his doctoral research at Tampere University within the Faculty of Medicine and Health Technology.
Public defence on Friday 19 December
The doctoral dissertation of MSc Mahmoud Gaballa in the field of Medicine and Bioscience titled Cardiac Ischemia On-a-Chip Using Human iPSC-Derived Cardiomyocytes will be publicly examined at the Faculty of Medicine and Health Technology, Tampere University, on Friday 19.12.2025. The Opponent will be Docent Riikka Martikainen, University of Eastern Finland. The Custos will be Professor Katriina Aalto-Setälä, Faculty of Medicine and Health Technology, Tampere University.