Vascular engineering using human embryonic stem cells

Engineering vascularized tissue constructs remains a major problem in regenerative medicine. The formation of such a microvasculature--like the vasculogenesis in early embryogenesis that it closely resembles--is guided by biochemical and biophysical cues, such as growth factors, extracellular matrix proteins, hypoxia, and hydrodynamic shear. As they undergo spontaneous and directed vascular differentiation, human embryonic stem cells can be used as a model system to explore central issues in engineering vascularized tissue constructs and, potentially, to elucidate vasculogenic and angiogenic mechanisms involved in such vascular diseases as limb and cardiac ischemia. Because the conventional spontaneous differentiation approach can only isolate small quantities of vascular cells, recent efforts have sought to develop controlled approaches, including the development of three-dimensional scaffolds to reengineer the microenvironments of early embryogenesis. This review focuses on emerging approaches to deriving and directing vasculatures from human embryonic stem cells and efforts to engineer 3D vasculatures from such derivatives.