Ex vivo priming of endothelial progenitor cells with SDF-1 before transplantation could increase their proangiogenic potential.
OBJECTIVE
As SDF-1 and its cognate receptor CXCR4 play a key role in the survival and mobilization of immature cells, we examined whether preconditioning of endothelial progenitor cells (EPCs) with SDF-1 could further promote their capacity to enhance angiogenesis.


RESULTS
EPC exposure to 100 ng/mL SDF-1 for 30 min induced a proangiogenic phenotype, with cell migration and differentiation into vascular cords in Matrigel and increased their therapeutic potential in a nude mouse model of hindlimb ischemia. This pretreatment enhanced EPC adhesion to activated endothelium in physiological conditions of blood flow by stimulating integrin-mediated EPCs binding to endothelial cells. Pretreated EPCs showed significantly upregulated surface alpha4 and alphaM integrin subunit expression involved in the homing of immature cells to a neovasculature and enhanced FGF-2 and promatrix metalloproteinase (MMP)-2 secretion. All these effects were significantly attenuated by EPC incubation with AMD-3100, a CXCR4 antagonist, by prior HSPGs disruption and by HUVEC incubation with anti-intercellular adhesion molecule1 (ICAM-1) and anti-vascular cell adhesion molecule (VCAM) blocking antibodies. Pretreated EPCs adhered very rapidly (within minutes) and were resistant to shear stresses of up to 2500 s(-1).


CONCLUSIONS
SDF-1 pretreatment during EPC expansion stimulates EPC adhesion to endothelial cells and thus augments the efficiency of cell therapy for ischemic vascular diseases.
Zemani
Faouzia
F
INSERM U765, Cardiovascular Research Center, Paris, France.
Silvestre
Jean-Sébastien
JS
Fauvel-Lafeve
Françoise
F
Bruel
Arlette
A
Vilar
José
J
Bieche
Ivan
I
Laurendeau
Ingrid
I
Galy-Fauroux
Isabelle
I
Fischer
Anne Marie
AM
Boisson-Vidal
Catherine
C
D000818:Animals; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology / Q000637:transplantation*; D006614:Hindlimb; D006801:Humans; D066298:In Vitro Techniques; D007511:Ischemia / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology*; D014183:Transplantation, Heterologous
C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D012333:RNA, Messenger; D019718:Receptors, CXCR4