Anifrolumab effectively decreased IFN-I secretion, attenuated hypoxia/reoxygenation-induced inflammation, and reduced oxidative stress in a human ventricular cardiac organoid model of I/R injury.
Does Anifrolumab reduce inflammation and oxidative stress in a human iPSC-derived ventricular cardiac organoid model of ischemia/reperfusion injury?
A novel human iPSC-derived ventricular cardiac organoid model co-cultured with macrophages successfully simulates myocardial ischemia/reperfusion injury and demonstrates the therapeutic potential of targeting the type I interferon pathway with Anifrolumab.
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.
Zhang et al. (Tue,) conducted a other in Myocardial ischemia/reperfusion (I/R) injury. Anifrolumab was evaluated on IFN-I secretion, inflammation, and oxidative stress. Anifrolumab effectively decreased IFN-I secretion, attenuated hypoxia/reoxygenation-induced inflammation, and reduced oxidative stress in a human ventricular cardiac organoid model of I/R injury.