Using stem cells to study atherosclerosis and Marfan syndrome

Vascular disease modelling using human pluripotent stem cell-derived smooth muscle cells

Smooth muscle cells (SMCs) in the blood vessel wall contribute to the ‘furring up’ of vessels in coronary heart disease and stroke. SMCs are also involved in an inherited condition known as Marfan syndrome, where a defect in fibrillin-1, a protein that provides structural support for the extracellular matrix that surrounds cells, leads to SMC death and ballooning and tearing of the aorta, the largest blood vessel in the body. As different parts of the same blood vessel may originate from distinct regions of the developing embryo, it is possible that the embryonic origin of cells influences development of disease. In this Senior Clinical Fellowship, Dr Sinha, working at the University of Cambridge, will test this idea by growing SMCs in a culture dish. He will use human stem cells or induced stem cells (derived from a patient’s skin) to generate SMCs that correspond to the three distinct embryonic regions that they originate from. He will test whether each of the three SMC subtypes has a different susceptibility to atherosclerosis by studying the cells and by generating artificial blood vessels in the laboratory. In addition, he will study the SMCs he has generated from people with Marfan syndrome. He will see if these SMCs look and behave differently from normal SMCs and will test drug-like small molecules on these cells to test if they have an effect. In this way, Dr Sinha will develop a model of studying Marfan syndrome in the laboratory.