Hard Luck Stories: The Reality of Endothelial Progenitor Cells Continues to Fall Short of the Promise

T he discovery of putative endothelial progenitor cells byAsahara and colleagues 1 engendered a new era of vascular biology, full of the promise of using circulating and bone marrow-derived progenitors for therapeutic angiogenesis.In this landmark article, Asahara et al demonstrated that a CD34 or Flk-1 positive fraction of mononuclear cells isolated from human peripheral blood formed endothelial tube-like structures in vitro and incorporated into capillaries in regions of ischemic injury.Thus, a new paradigm of "vasculogenesis in the adult" was born.Since this observation, more than a decade has gone by, with more than 8000 articles published on endothelial progenitors.2 Despite this extraordinary productivity, therapeutic vasculogenesis with endothelial progenitor cells continues to be in its infancy-a hard luck story, dogged by conflicting studies, lack of uniform criteria for defining an endothelial progenitor, and nonrigorous methods of determining progenitor-mediated vasculogenesis.