Therapeutic vasculogenesis: it takes two.

See related article, pages 194–202 The shortage of organs for transplantation has been so severe and prolonged that many of us have become almost numb to the crisis facing patients and their families. In 2008, there are 98 992 patients on various organ transplantation waiting lists in the United States alone; during January and February, 4471 transplants were performed but 1044 patients died while on waiting lists.1 This organ crisis shines an unwanted spotlight on the failure of tissue engineering to thus far deliver on its promises of the late 20th century. Tissue engineering in the 21st century still has the same potential, in some ways rediscovering itself under the more reputable moniker of “Regenerative Medicine.” However, some of the problems that kept tissue engineering from delivering the goods in the 1990s remain important ones in this century. One of the critical challenges in building any new organ is the dependence of an implanted tissue construct on sufficient oxygen and nutrient transport for its cells to survive, both for access to substrate molecules and clearance of products of metabolism.2 The principal mechanism for this transport, especially for small molecules, is passive diffusion along concentration gradients, and oxygen diffusion is of obvious importance. The transport of other nutrients is generally more favorable than that of oxygen because the diffusion of oxygen is relatively slow, consumption is high, and the tolerated time for any deficit is so short. To provide sufficient oxygen tension to mitochondria inside the cell, the minimum distance from the cell to the closest capillary lumen in many metabolically active tissues is rarely greater than 40 to 200 μm.3 With this proximity to flowing blood and its partial pressures of ≈100 mm Hg, oxygen can maintain the concentration gradient required at the cell. The distance-to-oxygen …