Dynamic haematopoietic cell contribution to the developing and adult epicardium.

The epicardium is a cellular source with the potential to reconstitute lost cardiovascular tissue following myocardial infarction. Here we show that the adult epicardium contains a population of CD45+ haematopoietic cells (HCs), which are located proximal to coronary vessels and encased by extracellular matrix (ECM). This complex tertiary structure is established during the regenerative window between post-natal days 1 and 7. We show that these HCs proliferate within the first 24 h and are released between days 2 and 7 after myocardial infarction. The ECM subsequently reforms to encapsulate HCs after 21 days. Vav1-tdTomato labelling reveals an integral contribution of CD45+ HCs to the developing epicardium, which is not derived from the proepicardial organ. Transplantation experiments with either whole bone marrow or a Vav1+ subpopulation of cells confirm a contribution of HCs to the intact adult epicardium, which is elevated during the first 24 weeks of adult life but depleted in aged mice.

Harnessing the potential of adult cardiac stem cells: lessons from haematopoiesis, the embryo and the niche.

Across biomedicine, there is a major drive to develop stem cell (SC) treatments for debilitating diseases. Most effective treatments restore an embryonic phenotype to adult SCs. This has led to two emerging paradigms in SC biology: the application of developmental biology studies and the manipulation of the SC niche. Developmental studies can reveal how SCs are orchestrated to build organs, the understanding of which is important in order to instigate tissue repair in the adult. SC niche studies can reveal cues that maintain SC 'stemness' and how SCs may be released from the constraints of the niche to differentiate and repopulate a 'failing' organ. The haematopoietic system provides an exemplar whereby characterisation of the blood lineages during development and the bone marrow niche has resulted in therapeutics now routinely used in the clinic. Ischaemic heart disease is a major cause of morbidity and mortality in humans and the question remains as to whether these principles can be applied to the heart, in order to exploit the potential of adult SCs for use in cardiovascular repair and regeneration.