title: Critical limb ischemia: thrombogenic evaluation of two autologous cell therapy products and biologic profile in treated patients.
abstract: BACKGROUND
  Cell therapy has been proposed as a salvage limb procedure in critical limb ischemia (CLI). Autologous cell therapy products (CTP) are obtained from patients with advanced peripheral arterial disease to be injected at the site of ischemia. Thrombogenicity of CTPs has not yet been assessed. The objectives were: 1) to assess thrombotic risk in candidates for cell therapy, 2) to evaluate two different CTPs in terms of thrombogenic potential, and 3) to evaluate clinical thrombotic events.
  
  
  METHODS
  In this ancillary study of a Phase I and II clinical trial, bone marrow (BM)-CTPs (n = 20) and CTPs obtained by cytapheresis (peripheral blood [PB]-CTPs; n = 20) were compared. Inflammatory and coagulation markers were measured at baseline and 24 hours after CTP implantation. CTP cell content and tissue factor (TF) expression (mRNA and protein) were analyzed. Thrombin generation assessed CTP-related thrombogenicity.
  
  
  RESULTS
  All patients presented cardiovascular risk factors. At baseline, the patients' biologic profile was characterized by high levels of fibrinogen, C-reactive protein (CRP), D-dimer, interleukin (IL)-6, and plasmatic TF, whereas IL-10 was low. Although different in terms of cell composition, both BM- and PB-CTPs support low thrombin generation. Twenty-four hours after implantation, biologic markers remained stable in the PB-CTP group, except for IL-6. In the BM-CTP group, a significant increase of IL-6 but also of CRP and D-dimer was observed. Clinically, one single patient developed deep vein thrombosis 24 hours after the implantation of autologous PB-CTP.
  
  
  CONCLUSIONS
  CTPs supported low thrombin generation and were well tolerated after calf implantation.
authors.affiliation: Laboratoire d'Hématologie, CHU Robert Debré, Reims.|EA-3801, SFR CAP-Santé, Université de Reims Champagne-Ardenne, Reims.
authors.forename: Claire
authors.initials: C
authors.lastname: Tournois
authors.affiliation: Unité de Thérapie Cellulaire, CHU, Reims, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Pignon
authors.affiliation: Service De Médecine Vasculaire, CHU, Amiens.
authors.forename: Marie-Antoinette
authors.initials: MA
authors.lastname: Sevestre
authors.affiliation: EA-3801, SFR CAP-Santé, Université de Reims Champagne-Ardenne, Reims.
authors.forename: Zoubir
authors.initials: Z
authors.lastname: Djerada
authors.affiliation: Laboratoire d'Hématologie, CHU, Amiens, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Capiod
authors.affiliation: EA-3801, SFR CAP-Santé, Université de Reims Champagne-Ardenne, Reims.
authors.forename: Gaël
authors.initials: G
authors.lastname: Poitevin
authors.affiliation: Laboratoire d'Hématologie, CHU Robert Debré, Reims.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Delloup
authors.affiliation: Laboratoire d'Hématologie, CHU Robert Debré, Reims.|EA-3801, SFR CAP-Santé, Université de Reims Champagne-Ardenne, Reims.
authors.forename: Philippe
authors.initials: P
authors.lastname: Nguyen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007511:Ischemia / Q000175:diagnosis* / Q000628:therapy; D007866:Leg / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow / Q000502:physiology