Differentiation and diversification of vascular cells from embryonic stem cells.

Pluripotent embryonic stem (ES) cells are potent materials for both regenerative therapeutic approaches and developmental research. Recently, a novel ES cell differentiation system combined with 2-dimensional culture and flow cytometry-assisted cell sorting has been developed. In this system, endothelial, mural, and blood cells can be systematically induced from common progenitor vascular endothelial growth factor receptor-2 (Flk1)-expressing cells. This system is amenable for the in vitro observation of multiple steps of the vascular developmental process, such as vascular cell differentiation and diversification from progenitors, endothelial cell maturation and differentiation into arterial, venous, and lymphatic endothelium, and vascular formation. This constructive in vitro approach provides novel possibilities for elucidating the cellular and molecular mechanisms of vascular development. Vascular cell induction from primate ES cells reveals primate-specific vascular developmental mechanisms. ES cell research in developmental biology would be indispensable, especially in the human species for which a knock-out animal model is not available. ES cells should also contribute to regenerative medicine, not only as a cellular source for transplantation but also for the discovery of novel genes and drugs for regeneration. In this review, the significance of ES cell study in basic science and clinical medicine in the vascular field is discussed.