Strategic development of stem cell-based therapies for vascular disease

Diseases of the heart and circulatory system are the main cause of death in the UK. While improvements in lifestyle are benefiting people at risk for these diseases, many already suffer from previous illness and others will nevertheless experience life-threatening episodes. Our work will strive to harness recent developments in the field of stem cell research to benefit those at risk for heart and circulatory diseases. This will be accomplished by studying the fundamental processes of cell growth, specialization and function that can be done in the Petri dish using modern microscopy and also by other imaging techniques. We will study cells that make up the normal and diseased heart and also those that form the lining and walls of the blood vessels. We expect our studies to provide the insights for future methods for diagnosis and treatment of lung disease and atherosclerosis, which together account for most cardiovascular disease risk.

Whilst stem cell research has great potential for translation into patient benefits, cell-based therapies are currently limited by lack of knowledge about human stem cell differentiation and about the extent and kinetics of integration and survival of transplanted tissues. Nonetheless, progeny obtained by in vitro differentiation of pluripotent stem cells can provide unprecedented cellular systems for understanding fundamental cardiovascular disease mechanisms, and for drug discovery and testing. Moreover, studies of endogenous tissue stem cells can provide key insights into their role in cardiovascular disease. We are establishing the Cambridge Cardiovascular Consortium to explore the interface between stem cells and cardiovascular medicine. The Consortium will focus on vascular disease, initially using pulmonary arterial hypertension (PAH) as a model, because its genetic basis is known, well-defined patient populations are available, and its molecular aetiology is highly relevant to other common vascular diseases, especially atherogenesis and vessel calcification. The strategic development of the Consortium will contribute great insight not only to PAH but also to vascular disease more broadly, and in future its infrastructure will serve studies of other cardiac and vascular diseases.