Phenotypic and Functional Characterization of Endothelial Colony Forming Cells Derived from Human Umbilical Cord Blood

Abstract

Longstanding views of new blood vessel formation via angiogenesis, vasculogenesis, and arteriogenesis have been recently reviewed 1 . The presence of circulating endothelial progenitor cells (EPCs) were first identified in adult human peripheral blood by Asahara et al. in 1997 2 bringing an infusion of new hypotheses and strategies for vascular regeneration and repair. EPCs are rare but normal components of circulating blood that home to sites of blood vessel formation or vascular remodeling, and facilitate either postnatal vasculogenesis, angiogenesis, or arteriogenesis largely via paracrine stimulation of existing vessel wall derived cells . No specific marker to identify an EPC has been identified, and at present the state of the field is to understand that numerous cell types including proangiogenic hematopoietic stem and progenitor cells, circulating angiogenic cells, Tie2 + monocytes, myeloid progenitor cells, tumor associated macrophages, and M2 activated macrophages participate in stimulating the angiogenic process in a variety of preclinical animal model systems and in human subjects in numerous disease states 4,5 . Endothelial colony forming cells (ECFCs) are rare circulating viable endothelial cells characterized by robust clonal proliferative potential, secondary and tertiary colony forming ability upon replating, and ability to form intrinsic in vivo vessels upon transplantation into immunodeficient mice [6][7][8] . While ECFCs have been successfully isolated from the peripheral blood of healthy adult subjects, umbilical cord blood (CB) of healthy newborn infants, and vessel wall of numerous human arterial and venous vessels [6][7][8][9]

Concise Review: Perspectives and Clinical Implications of Bone Marrow and Circulating Stem Cell Defects in Diabetes

“…Advances in the understanding of how blood cells develop from the hemogenic endothelium helps to interpret the hemato‐endothelial overlap of EPCs . Sophisticated culture protocols have clarified that the PB harbors even smaller populations of endothelial colony forming cells (ECFC), distinct from traditional EPCs . However, whether culture‐defined cell types truly exist in vivo or they represent in vitro artifacts is unknown.…”

LY2228820 Dimesylate, a Selective Inhibitor of p38 Mitogen-activated Protein Kinase, Reduces Angiogenic Endothelial Cord Formation in Vitro and in Vivo

“…1). Smooth muscle cells and endothelial cells are exposed to many growth factors and proinflammatory cytokines that contribute to angiogenesis, and p38 MAPK is implicated in downstream cytokine signaling (18,26); therefore, p38 MAPK signaling was analyzed in ECFCs, a subtype of umbilical cord blood-derived endothelial cells that can form intrinsic in vivo vessels upon transplantation into immunodeficient mice (27), and ADSCs, which are similar to mesenchymal stem cells, which can give rise to cells with pericytic properties that can stabilize vascular assembly in vitro (28). In ECFCs, there was a robust increase in VEGF-dependent phosphorylated p38 MAPK (p-p38) expression (p Ͻ 0.05), whereas bFGF, EGF, and IL-6 showed a modest (ϳ25%) increase in p-p38 by a highly sensitive immunoassay (Fig.…”

In Vitro Endothelialization of Biodegradable Vascular Grafts Via Endothelial Progenitor Cell Seeding and Maturation in a Tubular Perfusion System Bioreactor

“…In contrast, studies have shown that EPCs have improved proliferative potential. 10,11 Methods of isolation and largescale expansion of these cells have also been developed. [12][13][14] Early-and late-outgrowth EPCs have been implicated in the repair and function of the endothelium, and the harvest of these cells is less invasive than that of ECs.…”