title: Cell therapy in critical limb ischemia: A comprehensive analysis of two cell therapy products.
abstract: Cell therapy has been proposed as a salvage limb procedure in critical limb ischemia (CLI). In spite of the fact that clinical trials found some efficacy, the mechanism of action remains elusive. The objective of this study was to characterize two autologous cell therapy products (CTPs) obtained from patients with advanced peripheral arterial disease.
  
  
  
  Bone marrow (BM-CTPs) (n = 20) and CTPs obtained by non-mobilized cytapheresis (peripheral blood [PB]-CTPs) (n = 20) were compared. CTPs were characterized by their cell composition, by the quantification of endothelial progenitor cells (EPCs) and mesenchymal stromal cells (MSCs) and by transcriptomic profiling. The angiogenic profile and the 6-month outcome of CLI patients are described.
  
  
  
  Patients presented inflammation syndrome and high levels of CXCL12, soluble stem cell factor and granulocyte colony-stimulating factor, whereas granulocyte macrophage colony-stimulating factor was low. Circulating CD34+ cells represented rare events. BM and PB-CTPs were heterogeneous. Mature cells and colony-forming unit-endothelial cells were in higher concentration in PB-CTPs, whereas CD34+ stem cells and EPCs were more abundant in BM-CTPs. MSCs were identified in both CTPs. Transcriptomic profiling revealed the strong angiogenic potential of BM-CTPs. Transcutaneous partial pressure of oxygen, C-reative protein and neutrophil content in CTPs are predictive of the clinical outcome at 6 months.
  
  
  
  Transcriptomic allows an accurate characterization of CTPs. BM-CTPs have the richest content in terms of stem cells and transcriptome. The high content of mature cells in PB-CTPs means that they work via a paracrine mechanism. The clinical outcome indicates the deleterious influence the patients' status and the limits of an autologous approach. In this respect, MSCs may allow an allogenic strategy.
authors.affiliation: Laboratoire d'Hématologie, Centre Hospitalier Universitaire Robert Debré, Reims, France; Equipe d'accueil de recherche, Structure Fédératrice de Recherche Champagne Ardenne Picardie-Santé, Université de Reims Champagne-Ardenne, Reims, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Tournois
authors.affiliation: Unité de Thérapie Cellulaire, Centre Hospitalier Universitaire, Reims, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Pignon
authors.affiliation: Service de Médecine Vasculaire, Centre Hospitalier Universitaire, Amiens, France.
authors.forename: Marie-Antoinette
authors.initials: MA
authors.lastname: Sevestre
authors.affiliation: Equipe d'accueil de recherche, Structure Fédératrice de Recherche Champagne Ardenne Picardie-Santé, Université de Reims Champagne-Ardenne, Reims, France.
authors.forename: Rida
authors.initials: R
authors.lastname: Al-Rifai
authors.affiliation: Laboratoire d'Hématologie, Centre Hospitalier Universitaire Robert Debré, Reims, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Creuza
authors.affiliation: Equipe d'accueil de recherche, Structure Fédératrice de Recherche Champagne Ardenne Picardie-Santé, Université de Reims Champagne-Ardenne, Reims, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Poitevin
authors.affiliation: Equipe d'accueil de recherche, Structure Fédératrice de Recherche Champagne Ardenne Picardie-Santé, Université de Reims Champagne-Ardenne, Reims, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: François
authors.affiliation: Laboratoire d'Hématologie, Centre Hospitalier Universitaire Robert Debré, Reims, France; Equipe d'accueil de recherche, Structure Fédératrice de Recherche Champagne Ardenne Picardie-Santé, Université de Reims Champagne-Ardenne, Reims, France. Electronic address: pnguyen@chu-reims.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Nguyen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D016638:Critical Illness / Q000628:therapy*; D016238:Cytapheresis / Q000379:methods; D005121:Extremities / Q000098:blood supply*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D023821:Limb Salvage / Q000379:methods*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation; D000072916:Peripheral Blood Stem Cells / Q000166:cytology*
chemical_list: D016179:Granulocyte Colony-Stimulating Factor
keywords: angiogenesis; cell therapy; critical limb ischemia; endothelial progenitor cells; mesenchymal stem cells; transcriptome