Circulating and tissue resident endothelial progenitor cells

Abstract

Progenitor cells for the endothelial lineage have been widely investigated for more than a decade, but continue to be controversial since no unique identifying marker has yet been identified. This review will begin with a discussion of the basic tenets originally proposed for proof that a cell displays properties of an endothelial progenitor cell. We then provide an overview of the methods for putative endothelial progenitor cell derivation, expansion, and enumeration. This discussion includes consideration of cells that are present in the circulation as well as cells resident in the vascular endothelial intima. Finally, we provide some suggested changes in nomenclature that would greatly clarify and demystify the cellular elements involved in vascular repair.

Figure 1. Comparison of the phenotypic and functional characteristics of putative EPC determined by different assays

The cells isolated by the CFU-Hill and CAC assays identify essentially similar proangiogenic hematopoietic subsets. In contrast the cells isolated in the ECFC assay differ from the proangiogenic cells by displaying clonal proliferative potential, replating ability, and in vivo vessel forming ability. In addition the phenotype of the ECFC can be distinguished from the proangiogenic cells by the lack of CD133, CD45, and CD115 expression by the ECFC. Abbreviations: ALDH: aldehyde dehydrogenase, acLDL: acetylated low density lipoprotein, VEGFR2: vascular endothelial growth factor receptor 2.

Figure 2. Collaborative interaction of proangiogenic hematopoietic cells and ECFC in the formation of new blood vessels

Bone marrow-derived proangiogenic cells are recruited to sites of tissue ischemia or damaged endothelium and secrete paracrine molecules to recruit circulating and tissue resident ECFC to participate in new blood vessel formation.

Figure 3. Tissue specific and age-related differences in proliferative potential of endothelial cells

Rat pulmonary microvascular endothelial cells (PMVEC) and pulmonary arterial endothelial cells (PAEC) proliferate more rapidly than endothelial cells isolated from 9–11 day old rat kidney (RKEC young) and 8–10 week old adult rat kidney (RKEC adult). Modified from, Basile DP, et al. Microcirculation 19:598–609, 2012.