The Vasoreparative Potential of Endothelial Colony Forming Cells: A Journey Through Pre-clinical Studies

Abstract

For over a decade various cell populations have been investigated for their vasoreparative potential. Cells with the capacity to promote blood vessel regeneration are commonly known as endothelial progenitor cells (EPCs); although such a definition is currently considered too simple for the complexity of cell populations involved in the reparative angiogenic process. A subset of EPCs called endothelial colony forming cells (ECFCs) have emerged as a suitable candidate for cytotherapy, primarily due to their clonogenic progenitor characteristics, unequivocal endothelial phenotype, and inherent ability to promote vasculogenesis. ECFCs can be readily isolated from human peripheral and cord blood, expanded ex vivo and used to revascularize ischemic tissues. These cells have demonstrated efficacy in several in vivo preclinical models such as the ischemic heart, retina, brain, limb, lung and kidney. This review will summarize the current pre-clinical evidence for ECFC cytotherapy and discuss their potential for clinical application.

Keywords: angiogenesis; cell therapy; endothelial colony forming cells (ECFCs); endothelial progenitor cells (EPC); ischemia; vascular repair.

Figure 1

Properties of ECFCs. (A) ECFC cobblestone monolayer morphology (Scale bar 200 μm). (B) A tight monolayer of ECFCs with adherens junctions (β catenin = green, Vimentin = red, scale bar 100 μm). (C) A colony derived from a single cell demonstrating clonogenic potential of ECFCs (crystal violet stained, scale bar 200 μm). (D) ECFCs express endothelial markers CD31 & CD146 and are negative for hematopoietic markers CD14/45 and stromal marker CD90. (E) ECFCs have tubulogenic capacity in vitro (scale bar 200 μm) (F,G). ECFCs form perfused vessels in vivo in the Matrigel plug assay (Scale bar, 5 mm and 200 μm respectively).