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Myocardial inflammation modelling in iPSC-derived human cardiac organoids

  • 1 June 2023 to 29 February 2024
  • Awards: Pump-priming Awards

Award Holder: Dr Gintare Smagurauskaite, Division of Cardiovascular Medicine, RDM

The project aims to develop an in vitro model of human cardiac inflammation. Induced Pluripotent Stem Cells (iPSCs) will be differentiated into four major cardiac cell types (cardiomyocytes, endothelial cells, cardiac fibroblasts and vascular smooth muscle cells) which will be used to generate human myocardial organoids. Beating cardiac organoids will be treated with a range of pro-inflammatory substances in an attempt to recapitulate myocardial inflammation in humans. The inflammation will be characterised by performing proteomic analysis of the secreted cytokines, and by determining the ability of organoids to induce leukocyte chemotaxis. The preliminary data obtained from this project will support the development of organoid-based therapeutic screening protocols.

 

Immunofluorescence imaging of organoids stained with different cell type markers. There are three images of the same organoid on the left panel: DAPI stain in blue, α-Troponin in green, and α-Actinin in red. The overlay of these three stains is shown in an image on the bottom right. The overlay of DAPI in blue, PECAM1 in red and α-SMA in green is shown in the top right image.

Human cardiac organoid staining with cell-type specific markers. Organoids were mounted on glass slides and stained for the cardiomyocytes (α-Actinin and α-Troponin), endothelial cells (PECAM1), and vascular smooth muscle cells (α-SMA). The fluorescence was captured with Olympus SpinSR SoRa microscope.

Image credit: Dr Phalguni Rath, Dr James Bancroft and Edward Drydale.