Differentiation potential and functional properties of a CD34‑CD133+ subpopulation of endothelial progenitor cells

Abstract

Endothelial progenitor cells (EPCs) promote angiogenesis and play an important role in myocardial and vascular repair after ischemia and infarction. EPCs consist of different subpopulations including CD34- CD133+ EPCs, which are precursors of more mature CD34+CD133+ EPCs and functionally more active in terms of homing and endothelial regeneration. In the present study we analyzed the functional and differentiation abilities of CD34- CD133+ EPCs. Isolation of EPC populations (CD34+CD133+ , CD34- CD133+ ) were performed by specific multi-step magnetic depletion. After specific stimulation a significant higher adhesive and migrative capacity of CD34- CD133+ cells could be detected compared to CD34+CD133+ cells (P<0.001, respectively). Next to this finding, not only significantly higher rates of proliferation (P<0.005) were detected among CD34- CD133+ cells, but also a higher potential of cell-differentiation capacity into other cell types. Next to a significant increase of CD34- CD133+ EPCs differentiating into a fibroblast cell‑type (P<0.001), an enhancement into a hepatocytic cell-type (P=0.033) and a neural cell-type (P=0.016) could be measured in contrast to CD34+CD133+ cells. On the other hand, there was no significant difference in differentiation into a cardiomyocyte cell-type between these EPC subpopulations (P=0.053). These results demonstrate that EPC subpopulations vary in their functional abilities and, to different degrees, have the capacity to transdifferentiate into unrelated cell-types such as fibroblasts, hepatocytes, and neurocytes. This indicates that CD34- CD133+ cells are more pluripotent compared to the CD34+CD133+ EPC subset, which may have important consequences for the therapy of vascular diseases.