title: Autologous bone marrow mononuclear cell therapy improves symptoms in patients with end-stage peripheral arterial disease and reduces inflammation-associated parameters.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the effect of autologous bone marrow mononuclear cells (BM-MNCs) on symptoms and perfusion indices in severely symptomatic patients with peripheral arterial disease (PAD) without further option for endovascular or surgical revascularization.
  
  
  METHODS
  Only patients with severe symptomatic PAD (Fontaine class IIb-IV, Rutherford category 3-6) not amenable for revascularization were treated. Bone marrow from both cristae iliacae was harvested; MNCs were isolated by the Ficoll density-gradient method and transplanted by means of intra-arterial and intramuscular injection in the index limb. Functional (pain score, ulcer healing, maximum walking distance) and perfusion indices such as ankle-brachial-index and transcutaneous oxygen pressure were documented before and after BM-MNC therapy. Additionally, serum concentration of C-reactive protein and interleukin-6 were measured as markers of inflammation before and after BM-MNC treatment.
  
  
  RESULTS
  Sixteen consecutive patients (four women; mean age, 63.0 ± 13 years) were treated with a mean dose of 4.2 ± 2.2 × 10(8) BM-MNCs. At 6 months' follow-up, ankle-brachial-index, transcutaneous oxygen pressure and maximum walking distance significantly increased, whereas C-reactive protein and interleukin-6 conversely decreased (P < 0.01 versus baseline values), resulting in 88% limb salvage, 75% pain reduction and 71% complete wound healing and/or reduction of ulcer size. One major and one minor amputation were performed, both in patients with Rutherford category 6.
  
  
  CONCLUSIONS
  Autologous BM-MNC therapy in patients with end-stage PAD improves tissue perfusion indices and decreases markers of inflammation. If our observations could be confirmed by large-scale, randomized controlled trials, BM-MNC transplantation could become an alternative therapeutic option for patients with end-stage PAD.
authors: Division of Vascular Medicine, Department of Cardiovascular Medicine, University of Muenster, Muenster, Germany. Electronic address: nasser.malyar@ukmuenster.de.
authors: Nasser M
authors: NM
authors: Malyar
authors: Institute for Transfusion Medicine, University of Duisburg-Essen, Essen, Germany.
authors: Stefan
authors: S
authors: Radtke
authors: Department of Angiology, University of Duisburg-Essen, Essen, Germany.
authors: Khalil
authors: K
authors: Malyar
authors: Center of Angiology and Interventional Vascular Medicine, Agaplesion Bethesda Hospital Wuppertal, Germany.
authors: Jawed
authors: J
authors: Arjumand
authors: Institute for Transfusion Medicine, University of Duisburg-Essen, Essen, Germany.
authors: Peter A
authors: PA
authors: Horn
authors: Department of Angiology, HELIOS Klinik Krefeld, Germany.
authors: Knut
authors: K
authors: Kröger
authors: Division of Vascular Medicine, Department of Cardiovascular Medicine, University of Muenster, Muenster, Germany.
authors: Eva
authors: E
authors: Freisinger
authors: Division of Vascular Medicine, Department of Cardiovascular Medicine, University of Muenster, Muenster, Germany.
authors: Holger
authors: H
authors: Reinecke
authors: Institute for Transfusion Medicine, University of Duisburg-Essen, Essen, Germany.
authors: Bernd
authors: B
authors: Giebel
authors: Department of Angiology, University of Duisburg-Essen, Essen, Germany.
authors: Franz-Eduard
authors: FE
authors: Brock
mesh_terms: D000368:Aged; D001854:Bone Marrow Cells / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000379:methods*; D002097:C-Reactive Protein / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000502:physiology / Q000637:transplantation*; D023821:Limb Salvage; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000276:immunology / Q000628:therapy*; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014945:Wound Healing
chemical_list: D018836:Inflammation Mediators; D015850:Interleukin-6; D002097:C-Reactive Protein
keywords: autologous mononuclear cells; cell-based therapy; critical limb ischemia; end-stage peripheral arterial disease; inflammation