Endothelial progenitor cells in health and disease.

There is currently great excitement and expectation in the stem cell community following the discovery that multipotent stem cells can be cultured from human fetal tissue and retain their ability to give rise to a variety of differentiated cell types found in all three embryonic germ layers. Although the earliest sites of hematopoietic cell and endothelial cell differentiation in the yolk sac blood islands were identified about 100 years ago, cells with hemangioblast properties have not yet been identified in vivo. Endothelial cells differentiate from angioblasts in the embryo and from endothelial progenitor cells, mesoangioblasts and multipotent adult progenitor cells in the adult bone marrow. Circulating endothelial progenitor cells (EPC) have been detected in the circulation after vascular injury and during tumor growth. The molecular and cellular mechanisms underlying EPC recruitment and differentiation are not yet understood, and remain as one of the central issues in stem cell biology. For many years, the prevailing dogma stated that the vessels in the embryo develop from endothelial progenitors, whereas sprouting of vessels in the adult results only from division of differentiated endothelial cells. Recent evidence, however, indicates that EPC contribute to vessel growth in the embryo and in ischemic, malignant or inflammed tissues in the adult, and can even be therapeutically used to stimulate vessel growth in ischemic tissues.