Increase in vascular permeability and vasodilation are critical for proangiogenic effects of stem cell therapy.
BACKGROUND
Proangiogenic cell therapy based on administration of bone marrow-derived mononuclear cells (BMCs) or endothelial progenitor cells (EPCs) is now under investigation in humans for the treatment of ischemic diseases. However, mechanisms leading to the beneficial effects of BMCs and EPCs remain unclear.


RESULTS
BMC- and CD34+-derived progenitor cells interacted with ischemic femoral arteries through SDF-1 and CXCR4 signaling and released nitric oxide (NO) via an endothelial nitric oxide synthase (eNOS)-dependent pathway. BMC-induced NO production promoted a marked vasodilation and disrupted vascular endothelial-cadherin/beta-catenin complexes, leading to increased vascular permeability. NO-dependent vasodilation and hyperpermeability were critical for BMC infiltration in ischemic tissues and their proangiogenic potential in a model of hindlimb ischemia in mice.


CONCLUSIONS
Our results propose a new concept that proangiogenic progenitor cell activity does not rely only on their ability to differentiate into endothelial cells but rather on their capacity to modulate the function of preexisting vessels.
You
Dong
D
Cardiovascular Research Center, INSERM U689, Hopital Lariboisière, 41 boulevard de la chapelle, 75475 Paris Cedex 10, France.
Waeckel
Ludovic
L
Ebrahimian
Téni G
TG
Blanc-Brude
Olivier
O
Foubert
Philippe
P
Barateau
Véronique
V
Duriez
Micheline
M
Lericousse-Roussanne
Sophie
S
Vilar
José
J
Dejana
Elisabetta
E
Tobelem
Gérard
G
Lévy
Bernard I
BI
Silvestre
Jean-Sébastien
JS
D000818:Animals; D001158:Arteries / Q000473:pathology; D001854:Bone Marrow Cells; D002199:Capillary Permeability; D042783:Endothelial Cells; D006614:Hindlimb; D007511:Ischemia / Q000628:therapy*; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D009569:Nitric Oxide / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000379:methods*; D014664:Vasodilation
D009569:Nitric Oxide