Role of intimate interactions between endothelial cells and the surrounding accessory cells in the maturation of blood vessels

Summary.  While blood vessels clearly have a fundamental role in supplying oxygen and nutrients, and transporting inflammatory cells throughout the body, they are also involved in organogenesis and maintenance. Blood vessels provide a niche that supports self‐renewal of stem cell populations in normal organs. This role unfortunately also extends to the field of cancer biology; it has been suggested that cancer stem cells are located in perivascular regions supporting their proliferation. Through cell‐to‐cell interactions, arteries also have the important function of guiding appropriate migration of neurites. Therefore, analysis of the molecular mechanisms responsible for blood vessel formation and maintenance is important for developing strategies to regulate tissue regeneration. According to the usual concept of angiogenesis, it is widely accepted that homogeneous endothelial cells from preexisting vessels sprout and proliferate during angiogenesis. Recently, however, at least three different endothelial cell types designated tip, stalk and phalanx cells have been suggested to be involved in new blood vessel formation in sprouting angiogenesis. Given this endothelial cell heterogeneity, the involvement of a stem cell system in preexisting blood vessels is proposed. In addition, endothelial cells possess the capacity to differentiate into mesenchymal stem cells upon stimulation with growth factors, and pericytes show stem cell behaviour in their ability to differentiate into a variety of different histotypes. Moreover, under normal physiological conditions, haematopoietic stem cells differentiate into mural cells to provide blood vessel stability. These findings make it necessary to reconsider issues concerning the regulation of blood vessels by accessory cells situated around those vessels.