Nicola Smart - Development & Cell Biology - 'Developmental insights for cardiac regeneration'

We investigate mechanisms of embryonic heart formation to inform novel strategies to promote regeneration of the adult mammalian heart, for example after myocardial infarction. We have a particular interest in stimulating new coronary vessel growth and in the role of the outer layer epicardium in promoting neovascularisation and regeneration. Following injury, there is a partial recapitulation of embryonic processes that drive coronary vessel growth, yet fundamental differences in the regulatory pathways limit the efficacy of the adult response. Comparative analyses allow us to identify key mechanisms that may be targeted in the adult mammalian heart to enhance repair. Our research in murine models is complemented with the use of human iPSC-derived models of coronary vascular development. Due to their fundamental role in heart development, epicardium-derived cells (EPDCs) have emerged as a tractable progenitor population with potential to regenerate myocardium and coronary vasculature. Mobilisation of EPDCs into the adult myocardium requires the identification of “embryonic” stimuli that promote epicardial activation and mesenchymal transformation. Ongoing research therefore investigates the mechanisms controlling the transition from active (embryonic) to quiescent (adult) state, as well as the signalling pathways through which the embryonic epicardium stimulates expansion of the coronary vasculature.