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

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

  • Cell Prolif. 2024 Oct 8:e13762. doi: 10.1111/cpr.13762.
Laihai Zhang 1 2,  Yun Jiang 3,  Wenwen Jia 4,  Wenjun Le 3,  Jie Liu 1,  Peng Zhang 3 5,  Huangtian Yang 1 3 5,  Zhongmin Liu 1 2 3 6,  Yang Liu 1 3
Affiliations

Affiliations

  • 1 Shanghai Heart Failure Research Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 2 Department of Cardiovascular Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 3 Institute for Regenerative Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 4 National Stem Cell Translational Resource Center, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.
  • 5 Laboratory of Molecular Cardiology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences (CAS), Shanghai, China.
  • 6 Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, China.
PMID: 39377453 DOI: 10.1111/cpr.13762
Abstract

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.

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