Vascular Disease in a Dish

The emerging field of stem cell medicine offers unprecedented opportunities, among which the ability to model genetic diseases in vitro is one of the most exciting. In particular, disease modeling using stem cells promises to deliver a deeper understanding of disease mechanisms and to provide a test bed for novel therapies within a relatively short timeframe. The seminal discovery by Shinya Yamanaka only 6 years ago that somatic adult cells, such as fibroblasts taken from the skin, could be reprogrammed into cells that look and behave remarkably like embryonic stem cells1 has greatly accelerated progress toward these goals. These induced pluripotent stem cells (iPSCs), in common with their embryonic counterparts, possess the ability to self-replicate indefinitely yet also have the capacity to differentiate into almost any somatic cell type. Importantly, if derived from patients with overt disease, iPSCs will possess both the disease-causing mutation as well as the permissive genetic background that in many cases is required for full expression of the disease phenotype. In this issue of Circulation , Qyang and colleagues2 use this technology to increase our understanding of the vascular smooth muscle cell (SMC) pathology in supravalvular aortic stenosis (SVAS) and Williams-Beuren Syndrome (WBS)—conditions associated with reduced elastin expression and incorporation into the vascular wall.Article see p 1695Elastin is the predominant extracellular protein in elastic arteries, accounting for ≈33% of the dry weight of the aorta.3 It has key roles in conferring tensile and elastic properties and in regulating vascular SMC function. Nonsyndromic SVAS is caused by …