title: Early endothelial progenitor cells in bone marrow are a biomarker of cell therapy success in patients with critical limb ischemia.
abstract: OBJECTIVE
  Endothelial progenitor cells (EPC) have been proposed for autologous angiogenic therapy. The objectives of this study were to quantify EPC in the peripheral blood and bone marrow mononuclear cells (BM-MNC) of patients with critical limb ischemia that had received BM-MNC as a cell therapy product, and to study the putative relationship between the presence of EPC and the process of neovascularization in toe or transmetatarsal amputation specimens.
  
  
  METHODS
  Early and late endothelial progenitor cells (CFU-EC and ECFC) were cultivated and quantified according to published methods in peripheral blood and BM-MNC from patients with critical limb ischemia (CLI; n = 11) enrolled in the OPTIPEC trial ( http://clinicaltrials.gov/ct2/show/NCT00377897 ) to receive BM-MNC as a cell therapy product.
  
  
  RESULTS
  Eight out of the 11 patients had undergone amputations. Three of the patients displayed a neoangiogenic process that was associated with a higher number of CFU-EC in BM-MNC, while CD3+ , CFU-GM and CD34+ in BM-MNC, and EPC in peripheral blood, did not correlate with the appearance of newly formed vessels. As expected, circulating CFU-EC and ECFC counts were significantly lower in CLI patients compared with age-matched controls.
  
  
  CONCLUSIONS
  In patients with critical limb ischemia, EPC in peripheral blood were decreased compared with healthy individuals. However, in BM-MNC we found that relative numbers of CFU-EC could be used as an indicator to discriminate patients with neoangiogenic processes. These results need to be confirmed in a randomized study.
authors: Université Paris Descartes, Paris, France Sorbonne Paris Cite, France. david.smadja@egp.aphp.fr
authors: David M
authors: DM
authors: Smadja
authors: Jean-Paul
authors: JP
authors: Duong-van-Huyen
authors: Liliane
authors: L
authors: Dal Cortivo
authors: Anne
authors: A
authors: Blanchard
authors: Patrick
authors: P
authors: Bruneval
authors: Joseph
authors: J
authors: Emmerich
authors: Pascale
authors: P
authors: Gaussem
mesh_terms: D000368:Aged; D000671:Amputation, Surgical; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D042783:Endothelial Cells / Q000166:cytology* / Q000637:transplantation; D005121:Extremities / Q000473:pathology*; D006801:Humans; D007511:Ischemia / Q000473:pathology* / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers