Isolation of a nonmitogenic angiogenesis factor from wound fluid

Angiogenesis, or new capillary growth, is essential to normal growth and wound healing. It is also active in several pathologic states, including the growth of malignant tumors. An extracellular, nonneoplastic angiogenesis factor has been isolated from cell-free rabbit wound fluid by pore-limit dialysis and chromatography on a size-exclusion HPLC column. The isolated angiogenesis factor was purified 9,600-fold with a yield of 81% and has a molecular weight between 2,000 and 14,000. Wound fluid angiogenesis factor was completely separated from the mitogenic activity of wound fluid; it did not increase the number of capillary endothelial cells in vitro or stimulate [3H]thymidine uptake by these cells. The isolated angiogenesis factor stimulated endothelial cell migration in vitro, and less than 200 ng of the factor stimulated angiogenesis in vivo in the corneal implant assay.