EPC: the ischemia warrior of the bone marrow

Comment on Tepper et al, page 1068

Tepper and colleagues demonstrate that severe ischemia is the primary physiological trigger of circulating endothelial progenitor cell production by the bone marrow.

Bone marrow–derived endothelial progenitor cells (BM-EPCs) were first described a little over 5 years ago, ^1,2  heralding in a new paradigm of angiogenesis. Tepper and colleagues have developed a simple yet elegant new method to study the mechanisms of EPC production and recruitment from the bone marrow. One of the largest controversies surrounding BM-EPCs is why some models produce new vessels almost entirely derived from BM-EPCs³  and others produce vessels with significant yet low levels of EPC contribution.⁴  The new model induces a strong hypoxic gradient within a readily accessible skin flap that promotes predominantly BM-EPC–driven angiogenesis in the areas of the most severe ischemia, yet demonstrates very low BM-EPC contributions in areas with less ischemia (best highlighted in Figure 3C). The same contiguous new blood vessel is formed by different progenitor cells under differing levels of ischemia within the same skin flap. These exciting findings represent a simple elegant model that many can replicate and adopt to further delineate BM-EPC function. ▪FIG1