title: Combined autologous bone marrow mononuclear cell and gene therapy as the last resort for patients with critical limb ischemia.
abstract: BACKGROUND
  Our study was designed to investigate the safety and efficacy of combined autologous bone marrow mononuclear cell (MNC) and gene therapy in comparison to conventional drug therapy in patients with critical limb ischemia (CLI).
  
  
  METHODS
  Thirty-two patients with CLI persisting for 12-48 months (average time 27.5 months) were randomized into 2 groups, each group consisting of 16 patients. In the first group, administration of autologous bone marrow MNC and vascular endothelial growth factor (VEGF) plasmid was performed. The patients from the second group were treated pharmacologically with pentoxifylline. Ankle-brachial index (ABI) was measured and angiography was performed before and finally 3 months after treatment. The pain was evaluated using the Visual Analog Scale (VAS) before and after 3 months.
  
  
  RESULTS
  Ankle-brachial index improved significantly from 0.29 ±0.21 to 0.52 ±0.23 (p < 0.001) in 12 patients (75.0%) 3 months after the experimental therapy in group 1. In this group angiography showed the development of collateral vessels. Ischemic ulcers healed completely in 11 patients (68.75%). In group 2 the ABI did not improve in any patient; moreover the complete healing of skin ulcers was not found in any of the patients of this group. Amputation was performed in 4 (25.0%) patients in group 1, and in 8 patients (50%) from group 2.
  
  
  CONCLUSIONS
  These data after 3-month follow-up indicate that intramuscular injection of MNC combined with gene therapy in patients with chronic CLI is safe, and a more feasible and effective method of treatment than the conventional therapy. However, both therapies are limited by the degree of microcirculation damage.
authors.affiliation: Department of Vascular, General and Transplantation Surgery, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Skóra
authors.affiliation: Department of Vascular, General and Transplantation Surgery, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Pupka
authors.affiliation: Department of Clinical Procedures, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Janczak
authors.affiliation: Department of Vascular, General and Transplantation Surgery, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Barć
authors.affiliation: Department of Vascular, General and Transplantation Surgery, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Dawiskiba
authors.affiliation: Department of Vascular, General and Transplantation Surgery, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Korta
authors.affiliation: Department of Forensic Medicine, Molecular Techniques Unit, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Dagmara
authors.initials: D
authors.lastname: Baczyńska
authors.affiliation: Department of Family Medicine, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Mastalerz-Migas
authors.affiliation: Department of General Radiology, Interventional Radiology and Neuroradiology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Garcarek
keywords: atherosclerosis obliterans; critical limb ischemia; gene therapy; marrow stem cells