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