Direct comparison of umbilical cord blood versus bone marrow-derived endothelial precursor cells in mediating neovascularization in response to vascular ischemia.
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.
Finney
Marcie R
MR
Department of Medicine, Case Western Reserve University, School of Medicine, Case Comprehensive Cancer Center, Cleveland, Ohio 44106-7284, USA.
Greco
Nicholas J
NJ
Haynesworth
Stephen E
SE
Martin
Joseph M
JM
Hedrick
David P
DP
Swan
Jimmy Z
JZ
Winter
Daniel G
DG
Kadereit
Suzanne
S
Joseph
Matthew E
ME
Fu
Pingfu
P
Pompili
Vincent J
VJ
Laughlin
Mary J
MJ
D000328:Adult; D000818:Animals; D016026:Bone Marrow Transplantation; D002196:Capillaries / Q000648:ultrastructure; D002454:Cell Differentiation; D036101:Cord Blood Stem Cell Transplantation; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000166:cytology*; D005260:Female; D006614:Hindlimb / Q000098:blood supply*; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D007511:Ischemia / Q000503:physiopathology / Q000601:surgery*; D017078:Laser-Doppler Flowmetry; D008077:Lipoproteins, LDL / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018482:Muscle, Skeletal / Q000098:blood supply; D018919:Neovascularization, Physiologic / Q000502:physiology*; D037121:Plant Lectins / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism; D051116:Receptors, Scavenger / Q000378:metabolism; D013234:Stem Cells / Q000145:classification / Q000166:cytology; D017154:Stromal Cells / Q000166:cytology; D014183:Transplantation, Heterologous
D008077:Lipoproteins, LDL; D037121:Plant Lectins; D019718:Receptors, CXCR4; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger; C053203:Ulex europaeus lectin receptor; C036850:Ulex europaeus lectins; C032629:acetyl-LDL