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  • 1 July 2020 to 31 December 2021
  • Awards: Pump-priming Awards

The development of an efficient 3D induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) organoid cell culture has been challenging. This is in part due to the maturity of the iPSC-CMs. Several mechanisms have been highlighted to promote the maturity of CMs, including the interaction with endothelial cells. We will use a subtype of circulating endothelial progenitor cells (EPCs), endothelial colony-forming cells (ECFCs), to induce the maturation of iPSC-CMs in the organoid model. Substantial evidence implicates these late-outgrowth EPCs to have an active role in angiogenic remodelling, maintenance, and formation of vasculature in various physiological and pathophysiological conditions. Some studies have proposed that the plasticity of ECFCs can allow them to adopt organ-specific endothelial characteristics. Our preliminary unpublished data have shown that the co-culture of ECFCs and iPSC-CMs for organoid formation can be successful with the maintenance of cell-specific properties. In this project, we will develop preliminary data highlighting the potential interactions between ECFCs and iPSC-CMs and the maturity of the ECFC-CM organoids, which will be critical for establishing a matured-CM organoid platform. This could provide a robust and accurate in-vitro disease model and drug-testing platform, more closely mimicking human cardiac physiology in-vitro, which could have multiple applications across research groups.

Image title: Immunofluorescent imaging of a 3D endothelial colony forming cell and human iPSC-cardiomyocyte organoid structure

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