Direct Comparison of Umbilical Cord Blood versus Bone Marrow–Derived Endothelial Precursor Cells in Mediating Neovascularization in Response to Vascular Ischemia

Abstract

Endothelial precursor cells (EPCs) cultured from adult bone marrow (BM) have been shown to mediate neovasculogenesis in murine models of vascular injury. We sought to directly compare umbilical cord blood (UCB)- and BM-derived EPC surface phenotypes and in vivo functional capacity. UCB and BM EPCs derived from mononuclear cells (MNC) were phenotyped by surface staining for expression of stromal (Stro-1, CXCR4, CD105, and CD73), endothelial (CD31, CD146, and vascular endothelial [VE]-cadherin), stem cell (CD34 and CD133), and monocyte (CD14) surface markers and analyzed by flow cytometry. The nonobese diabetic/severe combined immunodeficiency murine model of hind-limb ischemia was used to analyze the potential of MNCs and culture-derived EPCs from UCB and BM to mediate neovasculogenesis. Histologic evaluation of the in vivo studies included capillary density as a measure of neovascularization. Surface CXCR4 expression was notably higher on UCB-derived EPCs (64.29%+/-7.41%) compared with BM (19.69%+/-5.49%; P=.021). Although the 2 sources of EPCs were comparable in expression of endothelial and monocyte markers, BM-derived EPCs contained higher proportions of cells expressing stromal cell markers (CD105 and CD73). Injection of UCB- or BM-derived EPCs resulted in significantly improved perfusion as measured by laser Doppler imaging at days 7 and 14 after femoral artery ligation in nonobese diabetic/severe combined immunodeficiency mice compared with controls (P<.05). Injection of uncultured MNCs from BM or UCB showed no significant difference from control mice (P=.119; P=.177). Tissue samples harvested from the lower calf muscle at day 28 demonstrated increased capillary densities in mice receiving BM- or UCB-derived EPCs. In conclusion, we found that UCB and BM-derived EPCs differ in CXCR4 expression and stromal surface markers but mediate equivalent neovasculogenesis in vivo as measured by Doppler flow and histologic analyses.

Multipotent adult progenitor cells sustain function of ischemic limbs in mice

“…The differences between our results and those in the cranial window model may be due to the different tissue environments in the 2 models. Similar to mMAPC-VP and in line with other studies (7,38,39), injection of mBMCs resulted in vascular bed expansion and improved perfusion and function of hind limb muscles; however, this too was temporary and less pronounced compared with mMAPC-U. Whether the lack of direct contribution of mBMCs to vessels and muscle tissue, or mMAPC-VP to skeletal muscle or their lower level of engraftment, underlies the significantly lower degree of improvement in perfusion or swim endurance compared with that of mMAPC-U remains to be determined.…”

CD133 positive progenitor endothelial cell lines from human cord blood

“…Its role was studied in HSCs differentiation and migration (23) as well as in cancer cells spreading (24). In the case of EPCs, a higher expression of CXCR4 was found on EPCs separated from umbilical cord blood than those coming from bone marrow (25). CD44 presents a variety of forms that modulate its activity in various cellular functions including lymphocyte activation, adhesion, recirculation, and homing.…”

Chemokine receptor CXCR4-prognostic factor for gastrointestinal tumors

“…On the one side, SDF-1α and VEGFB attract endothelial precursor cells towards the tumor. On the other side, hemangiocytes (VEGFR1 + , CXCR4 + ) are released in the bone marrow by VEGFA and directed towards the tumor by a SDF-1α gradient, where they might differentiate to pericytes stabilizing the neo-vasculature [25,26] . In contrast to benign tissues, tumors often reveal a significant up-regulation of CXCR4.…”