Human adult vena saphena contains perivascular progenitor cells endowed with clonogenic and proangiogenic potential

P Campagnolo, D Cesselli, A Al Haj Zen, AP Beltrami, N Kraenkel, RG Katare, G Angelini, C Emanueli, PR Madeddu

Research output: Contribution to journalArticle (Academic Journal)peer-review

219 Citations (Scopus)

Abstract

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.

METHODS AND 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.

Translated title of the contributionHuman adult vena saphena contains perivascular progenitor cells endowed with clonogenic and proangiogenic potential
Original languageEnglish
Pages (from-to)1735 - 1745
Number of pages10
JournalCirculation
Volume121
Issue number15
DOIs
Publication statusPublished - 20 Apr 2010

Bibliographical note

Publisher: Circulation

Keywords

  • Adult
  • Adult Stem Cells
  • Animals
  • Antigens, CD31
  • Antigens, CD34
  • Cell Separation
  • Cells, Cultured
  • Clone Cells
  • Coronary Artery Bypass
  • Disease Models, Animal
  • Flow Cytometry
  • Graft Survival
  • Hematopoietic Stem Cell Transplantation
  • Hindlimb
  • Humans
  • Injections, Intramuscular
  • Ischemia
  • Male
  • Mesenchymal Stromal Cells
  • Mice
  • Mice, Mutant Strains
  • Mice, Nude
  • Neovascularization, Physiologic
  • Saphenous Vein

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