Human Adult Vena Saphena Contains Perivascular Progenitor Cells Endowed With Clonogenic and Proangiogenic Potential

• Published in: Circulation (New York, N.Y.) Vol. 121; no. 15; pp. 1735 - 1745
• Main Authors: CAMPAGNOLO, Paola, CESSELLI, Daniela, AYMAN AL HAJ ZEN, BELTRAMI, Antonio Paolo, KRÄNKEL, Nicolle, KATARE, Rajesh, ANGELINI, Gianni, EMANUELI, Costanza, MADEDDU, Paolo
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 20-04-2010
• Subjects: Adult; Adult Stem Cells - cytology; Adult Stem Cells - metabolism; Animals; Antigens, CD34 - metabolism; Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Cardiology. Vascular system; Cell Separation - methods; Cells, Cultured; Clone Cells - cytology; Coronary Artery Bypass; Disease Models, Animal; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Graft Survival; Hematopoietic Stem Cell Transplantation - methods; Hindlimb - blood supply; Humans; Injections, Intramuscular; Ischemia - pathology; Ischemia - therapy; Male; Medical sciences; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Mice; Mice, Mutant Strains; Mice, Nude; Neovascularization, Physiologic - physiology; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Saphenous Vein - cytology; Vertebrates: cardiovascular system; Human; CD34 antigen; Angiogenesis; Pericyte; Treatment; Ischemia; cell therapy; pericytes; angiogenesis factors; Cardiovascular disease; Progenitor cell
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.109.899252

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.
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.
SVPs generated from human vein CD34-positive/CD31-negative progenitor cells might represent a new therapeutic tool for angiogenic therapy in ischemic patients.