Human adult vena saphena contains perivascular progenitor cells endowed with clonogenic and proangiogenic potential.
BACKGROUND
Clinical trials in ischemic patients showed the safety and benefit of autologous bone marrow progenitor cell transplantation. Non-bone marrow progenitor cells with proangiogenic capacities have been described, yet they remain clinically unexploited owing to their scarcity, difficulty of access, and low ex vivo expansibility. We investigated the presence, antigenic profile, expansion capacity, and proangiogenic potential of progenitor cells from the saphenous vein of patients undergoing coronary artery bypass surgery.


RESULTS
CD34-positive cells, negative for the endothelial marker von Willebrand factor, were localized around adventitial vasa vasorum. After dissection of the vein from surrounding tissues and enzymatic digestion, CD34-positive/CD31-negative cells were isolated by selective culture, immunomagnetic beads, or fluorescence-assisted cell sorting. In the presence of serum, CD34-positive/CD31-negative cells gave rise to a highly proliferative population that expressed pericyte/mesenchymal antigens together with the stem cell marker Sox2 and showed clonogenic and multilineage differentiation capacities. We called this population "saphenous vein-derived progenitor cells" (SVPs). In culture, SVPs integrated into networks formed by endothelial cells and supported angiogenesis through paracrine mechanisms. Reciprocally, endothelial cell-released factors facilitated SVP migration. These interactive responses were inhibited by Tie-2 or platelet-derived growth factor-BB blockade. Intramuscular injection of SVPs in ischemic limbs of immunodeficient mice improved neovascularization and blood flow recovery. At 14 days after transplantation, proliferating SVPs were still detectable in the recipient muscles, where they established N-cadherin-mediated physical contact with the capillary endothelium.


CONCLUSIONS
SVPs generated from human vein CD34-positive/CD31-negative progenitor cells might represent a new therapeutic tool for angiogenic therapy in ischemic patients.
Campagnolo
Paola
P
Division of Experimental Cardiovascular Medicine, Bristol Heart Institute, University of Bristol, Bristol, United Kingdom.
Cesselli
Daniela
D
Al Haj Zen
Ayman
A
Beltrami
Antonio Paolo
AP
Kränkel
Nicolle
N
Katare
Rajesh
R
Angelini
Gianni
G
Emanueli
Costanza
C
Madeddu
Paolo
P
D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D002999:Clone Cells / Q000166:cytology; D001026:Coronary Artery Bypass; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007273:Injections, Intramuscular; D007511:Ischemia / Q000473:pathology / Q000628:therapy*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012501:Saphenous Vein / Q000166:cytology*
D018952:Antigens, CD34; D019408:Platelet Endothelial Cell Adhesion Molecule-1