Date of Award
5-10-2026
Date Published
June 2026
Degree Type
Thesis
Degree Name
Master of Science (MS)
Department
Biomedical and Chemical Engineering
Advisor(s)
Zhen Ma
Keywords
Calcium transient;Cardiac organoids;Cardioids;hiPSC;Inflammatory cardiotoxicity;Mitochondrial dysfunction
Abstract
Inflammation plays a complex dual role in the pathology of cardiovascular diseases. Therefore, the precise regulation of inflammatory processes is a core challenge in the treatment of cardiopathy. To explore the complex effects of inflammation on cardiac function and structure, it is critical to develop human-relevant in vitro models with high physiological relevance. Human-induced pluripotent stem cells (hiPSCs) derived cardioids provide an effective research platform for modeling. This study aimed to establish an in vitro model of cardiac inflammation using hiPSCs-induced cardioids and to characterize their functional changes. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and lipopolysaccharide (LPS) were used to induce inflammatory responses in cardioids. We evaluated (1) key pathways of cell injury, including apoptosis, ROS production, mitochondrial function, and glycolysis; and (2) functional outcomes, including contractility and calcium transient kinetics. Our results suggest that specific cytokines, in particular TNF-α and IL-1β, induce significant cellular stress. In addition, we observed severe metabolic disorders caused by TNF-α and LPS, characterized by reduced mitochondrial membrane potential and impaired glycolytic function. Further analysis showed that macroscopic contractile motion was mostly preserved under the tested conditions, whereas calcium transient parameters displayed time-dependent and stimulus-dependent alterations. These findings suggest a limited correspondence between calcium-handling changes and macroscopic contractile output, which warrants further mechanistic investigation. In conclusion, this study established a hiPSC-derived cardioid model for studying inflammation-associated cardiac injury and demonstrated its potential as a platform for investigating cellular stress, metabolic dysfunction, and functional responses in human 3D cardiac microtissues.
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Recommended Citation
Liu, Huiyao, "Modeling Cardiac Inflammation in Human iPSC-Driven Cardioids" (2026). Theses - ALL. 1016.
https://surface.syr.edu/thesis/1016
