Angiogenesis inhibitors have become essential tools in the treatment of diseases such as cancer, age-related macular degeneration, psoriasis, and diabetic retinopathy (reviewed in [1]), making angiogenesis a clinically relevant target process for drug discovery. For example, solid tumors require an adequate supply of blood vessels in order to survive, grow, and metastasize [2, 3]. Recently, a link between angiogenesis and Alzheimer's disease has also been postulated [4], possibly highlighting another clinical use for antiangiogenesis drugs.

Multiple in vitro and in vivo angiogenesis assays are commonly used for drug discovery. Each of these assays has distinct advantages and disadvantages [5 –7]. In vitro endothelial cell models of migration, proliferation, apoptosis, and tube formation are popular because of their simplicity and throughput. However, most of these models address only the effects of compounds on endothelial cells and not other tissues in the vascular bed, such as smooth muscle cells, fibroblasts, and endothelial progenitor cells. Because angiogenesis involves the proliferation and migration of endothelial cells in the context of a living organism, current in vitro models employed in screening campaigns may prove vulnerable to a variety of unanticipated limitations.