Lumen formation: in vivo versus in vitro observations

Lumen formation must accompany the de novo growth of blood vessels during embryological development, the production of new vessels (vasculogenesis), and the expansion or remodeling of the microcirculation in differentiated tissue (angiogenesis). The debate over lumen origin centers on whether this is an intracellular or intercellular phenomenon, entailing vesicle accretion or loss of endothelial cell (EC) contact, and whether this represents an intrinsic property of ECs or relies on extrinsic signals. In addition, recent in vivo data suggest that a third mechanism, that of longitudinal division, may be used to expand existing capillary networks. Importantly, more than one mechanism of lumen formation may be found in response to a given angiogenic signal. Tubule formation by ECs in a matrix is an increasingly popular form of in vitro angiogenesis assay, and it may offer insights into the mechanisms involved during growth in embryos or under pathological conditions in adults. Crucial to the validity of in vitro preparations is the extent to which tubule assembly and lumen formation mirrors that observed in vivo, although these data cannot elucidate the controls operative during adaptive remodeling of the vascular bed. Similar structures may be observed in vivo and in vitro, and may represent the situation found during angiogenesis and vasculogenesis, respectively. Lumen formation during angiogenesis, and tubule formation during EC culture, require the existence of cell polarity. As tubule formation is not a unique property of ECs, how this is developed is a key area where in vitro studies may extend our understanding of EC biology.