title: Autologous bone marrow stem cell transplantation in critical limb ischemia: a meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Amputation-free survival (AFS) has been recommended as the gold standard for evaluating No-Option Critical Limb Ischemia (NO-CLI) therapy. Early-phase clinical trials suggest that autologous bone-marrow derived cells (BMCs) transplantation may have a positive effect on patients with NO-CLI, especially decreasing the incidence of amputation. However, the BMCs therapeutic efficacy remains controversial and whether BMCs therapy is suitable for all CLI patients is unclear.
  
  
  METHODS
  We conducted a meta-analysis using data from randomized controlled trials (RCTs) by comparing autologous BMCs therapy with controls in patients with critical limb ischemia, and the primary endpoint is the incidence of amputation. Pubmed, EBSCO and the Cochrane Central Register of Controlled Trials (to approximately July 25, 2012) were searched.
  
  
  RESULTS
  Seven RCTs with 373 patients were enrolled in the meta-analysis. Because serious disease was the main reason leading to amputation in one trial, six studies with 333 patients were finally included in the meta-analysis. Pooling the data of the final six studies, we found that BMCs therapy significantly decreased the incidence of amputation in patients with CLI (odds ratio (OR), 0.37; 95% confidence interval (CI), 0.22 to 0.62; P = 0.0002), and the efficacy had not significantly declined within 6 months after BMCs were transplanted; OR, 0.33; 95%CI, 0.16 to 0.70; P = 0.004 within 6 months and OR, 0.30; 95%CI, 0.11 to 0.79; P = 0.01 within 3 months. The rate of AFS after BMCs therapy was significantly increased in patients with Rutherford class 5 CLI (OR 3.28; 95%CI, 1.12 to 9.65; P = 0.03), while there was no significant improvement in patients with Rutherford class 4 (OR 0.35; 95%CI, 0.05 to 2.33; P = 0.28) compared with controls. The BMCs therapy also improved ulcer healing (OR, 5.83; 95%CI, 2.37 to 14.29; P = 0.0001).
  
  
  CONCLUSIONS
  Our analysis suggests that autologous BMCs therapy has a beneficial effect in decreasing the incidence of amputation and the efficacy does not decrease significantly within 6 months after BMCs transplantation. Patients with Rutherford class 5 are suitable for BMCs therapy, while the efficiency in patients with Rutherford 4 needs further evaluation.
authors.affiliation: Division of Endocrinology, Department of Medicine, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, China.
authors.forename: Fu-Peng
authors.initials: FP
authors.lastname: Liu
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Dong
authors.forename: Shu-Juan
authors.initials: SJ
authors.lastname: Sun
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Gao
authors.forename: Zhong-Wen
authors.initials: ZW
authors.lastname: Zhang
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Zhou
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.forename: Jun-Yu
authors.initials: JY
authors.lastname: Zhao
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Yao
authors.forename: Meng
authors.initials: M
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Liao
mesh_terms: D016026:Bone Marrow Transplantation / Q000379:methods*; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D035002:Lower Extremity / Q000473:pathology*; D016032:Randomized Controlled Trials as Topic; D014182:Transplantation, Autologous / Q000379:methods*