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Repair of the heart by stem cells protected with new drugs

Research Unit: Cytoprotection Pharmacology
Primary Supervisor: Dr Hitesh Peshavariya and Professor Greg Dusting
Tel: +613 9929 8143 or 8078 / Email: hitesh.peshavariya@unimelb.edu.au

Heart attack is a sudden catastrophic event in the lives of many people and heart failure is still one of the leading causes of death in Australia and worldwide. After heart attack the body responds to attempt repair by stimulating existing stem cells (called regenerative or progenitor cells) in the blood and bones. Attempts have been made to repair heart muscle using drugs to mobilise regenerative cells in order to prevent progression to heart failure, but these trials had limited success in the clinic. A major hurdle has been that mobilised regenerative cells are insufficient for heart repair in aged people and patients with other cardiovascular diseases such as hypertension, stroke and diabetes. Endothelial progenitor cells (EPCs) play an important role in repair of cardiovascular diseases. In this project we will test whether prostacyclin enhances mobilisation and survival of transplanted EPCs after myocardial infarction in mice.

We will study the intracellular mechanisms of prostacyclin signalling in endothelial progenitor cells and its role in cell mobilisation, homing and differentiation processes, which are all involved in promoting neovascularisation. We will then evaluate blood vessel formation in vivo using endothelial progenitor cell therapy and pharmacological intervention, which modulates prostacyclin signalling, in terms of their contributions to neovascularisation. These studies will use pharmacological, molecular and cell culture tools as well as knockout mice, and mouse models of myocardial infarction.

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