Biological surgery: synergetic angiogenic therapy using coadministration of two progenitor cell populations.

See related article, pages 751–760 Despite the many therapeutic breakthroughs in cardiovascular science, ischemic coronary and peripheral vascular diseases are still a major health problem throughout the world, and many patients do not respond or are not candidates for available medical and/or surgical treatments. Recently, identification of adult progenitor cells capable of contributing to tissue regeneration has raised the possibility that cell-based therapy could be used for the repair of ischemic heart or limb. There is compelling evidence that circulating endothelial progenitor cells (EPCs) play a role in tissue repair after a myocardial infarction, and higher levels of circulating EPCs are predictive of better short and long-term outcomes.1 EPCs were initially described as a subset of CD34+ hematopoietic stem cells that coexpress vascular endothelial growth factor receptor-2 (VEGFR-2), also known as Flk-1 or KDR. VEGFR-2–positive cells derived from embryonic stem cells can differentiate into both endothelial cells and smooth muscle cells, reproducing the vascular organization process.2 Smooth muscle progenitor cells (SMPCs) were identified more recently and reported to be present in bone marrow, circulating blood, vascular adventitia, and other tissues.3,4 Both EPCs and SMPCs can be mobilized by stromal cell–derived factor-1, a chemokine whose expression increases in response to tissue hypoxia based on regulation by the transcription factor, hypoxia-inducible factor-1,5 suggesting that EPCs and SMPCs may play pivotal roles in repairing injury to the vascular network. In addition, several cell types, including bone marrow cells, embryonic EPCs, and mesenchymal stem cells, have been tested in vivo for their effect on restoring blood supply and/or muscle function in ischemic heart and limbs. The …