Endothelial progenitor cells - Vasculogenesis

Endothelial Progenitor Cells (EPCs) are immature cells. They have the capacity to proliferate, migrate and differentiate in to endothelial lineage cells.  Hematopoietic stem cells and EPCs are derived from the common precursor (hemangioblast). These two stem cells share similar surface marker antigens. They are Flk-1, Tie-2, c-Kit, Sca-1, AC133 (CD133) and CD34+.

It was interesting to note that in 1997 Asahara et al found the importance of CD34+ cells in the neovasculogenesis.  The antigens expressed on the surface differentiate the HSCs and EPCs from the leukocyte fraction of peripheral blood. CD34+ is expressed by all the HSCs but lost by the differentiated hematopoietic cells.

It was believed that the post natal neovascularisation (angiogenesis) is possible by the proliferation, migration, remodelling of the fully differentiated endothelial cells. Vasculogenesis was considered to be formation of embryonic blood vessels from the EPCs or angioblasts. Vasculogenesis begins as a cluster formation or blood island comprising angioblasts at the periphery and HSCs at the center. So, demonstration of HSCs and EPCs in the peripheral blood based on the surface antigens on them proves the fact that there are stem cells circulating in peripheral blood and they are involved in the neovasculogenesis. A potentially limiting factor in strategies designed to promote neovascularisation of ischemic tissues is the resident population of ECs, that is competent to respond to administered angiogenic cytokines.

Asahara et al felt that this issue may be successfully addressed with autologous EC transplants. The fact that progenitor ECs home to foci of angiogenesis suggests potential utility as autologous vectors for gene therapy. For antineoplastic therapies, MBCD34+ cells could be transfected with or coupled to antitumor drugs or angiogenesis inhibitors. For treatment of regional ischemia, angiogenesis could be amplified by transfection of MBCD34+ cells to achieve constitutive expression of angiogenic cytokines or provisional matrix proteins or both. In a recent study by Turan et al have shown that the circulating EPCs were reduced in patients with extensive coronary artery disease (3 vessel disease / SYNTAX score >33). We may need to understand more about this fact and bring to this point from bench to the routine bed side management of patients.

References

Asahara T, Murohara T, Sullivan  A  et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997; 275:964-967

Turan RG, Turan Ch, Bozdag-Turam I et al. Impaired mobilization of CD 133+bone derived circulating progenitor cells with an increased number of diseased coronary arteries in ischemic heart disease patients with diabetes. Circ J 2011; 75:2635-2641