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Jarmon Lees

St Vincent's Institute of Medical Research

Dr. Jarmon Lees completed his PhD at the University of Melbourne in 2017 where he examined the role of metabolism in regulating human pluripotent stem cell pluripotency and neural differentiation. He then worked on the development of a novel pluripotent stem cell growth formulation for the biotech company Vitrolife. In 2018, Jarmon joined the Cardiac Regeneration Group at St Vincent’s as a Research Fellow examining cardiomyopathy in Friedreich’s ataxia and strategies for innervating human cardiac tissue using pluripotent stem cells. The cardiac regeneration lab is involved in modeling a range of heart diseases using a novel vascularised and innervated cardiac organoid model. 


Heart disease in a dish: human iPSC-derived multicellular cardiac organoids  

Abstract:

Cardiovascular disease is the leading cause of death worldwide necessitating accurate human disease models to improve our cellular and molecular understanding of heart diseases and facilitate preclinical trials. Here we have developed an advanced 3D multicellular human heart tissue model for modelling cardiovascular diseases. Human induced pluripotent stem cells (iPSCs) were differentiated into cardiomyocytes, endothelial cells and sympathetic neurons for construction of vascularised and innervated cardiac organoids, which can be maintained for at least 4 weeks in culture. Histological analysis showed CD31+ endothelial networks and tyrosine hydroxylase+ neural networks interspersed throughout the organoids. Single-cell RNAseq showed reproducibility of our cardiac organoids containing all input cell types and cells in an intermediate state. Cardiac organoids exhibited spontaneous and synchronous contractions at ~160 bpm. Subjecting the cardiac organoid to an acute ischaemia-reperfusion injury or chronic hyperglycaemic and hyperlipidaemic (to simulate type 2 diabetes) conditions increased the release of lactate dehydrogenase (an indicator of cell death). Cardiac organoids subjected to chronic hyperglycaemia and hyperlipidaemia also showed a reduction in contraction rate and prolongation in relaxation time. This indicates the capability of the cardiac organoids to simulate cardiac responses to ischaemic heart disease and type 2 diabetes-induced cardiac injury. This in vitro human cardiac tissue will be an ideal pre-clinical human model to study and develop novel therapeutics for heart diseases.