Modelling myocardial ischemia/reperfusion injury with inflammatory response in human ventricular cardiac organoids

作者：Laihai Zhang, Yun Jiang, Wenwen Jia, Wenjun Le, Jie Liu, Peng Zhang, Huang‐Tian Yang, Zhongmin Liu, Yang Liu · 发表于：Cell Proliferation · 年份：2024 · DOI：10.1111/cpr.13762 · 被引用次数：21 · 研究领域：Cardiac Fibrosis and Remodeling、Fuel Cells and Related Materials、Mechanical Circulatory Support Devices

Current therapeutic drug exploring targeting at myocardial ischemia/reperfusion (I/R) injury is limited due to the lack of humanized cardiac models that resemble myocardial damage and inflammatory response. Herein, we develop ventricular cardiac organoids from human induced pluripotent stem cells (hiPSCs) and simulate I/R injury by hypoxia/reoxygenation (H/R), which results in increased cardiomyocytes apoptosis, elevated oxidative stress, disrupted morphological structure and decreased beat amplitude. RNA-seq reveals a potential role of type I interferon (IFN-I) in this I/R injury model. We then introduce THP-1 cells and reveal inflammatory responses between monocytes/macrophages and H/R-induced ventricular cardiac organoids. Furthermore, we demonstrate Anifrolumab, an FDA approved antagonist of IFN-I receptor, effectively decreases IFN-I secretion and related gene expression, attenuates H/R-induced inflammation and oxidative stress in the co-culture system. This study advances the modelling of myocardial I/R injury with inflammatory response in human cardiac organoids, which provides a reliable platform for preclinical study and drug screening.