title: Bone Marrow derived Cell Therapy in Critical Limb Ischemia: A Meta-analysis of Randomized Placebo Controlled Trials.
abstract: OBJECTIVE
  Critical limb ischemia (CLI) is the most advanced stage of peripheral artery disease (PAD), and many patients with CLI are not eligible for conventional revascularization. In the last decade, cell based therapies have been explored as an alternative treatment option for CLI. A meta-analysis was conducted of randomized placebo controlled trials investigating bone marrow (BM) derived cell therapy in patients with CLI.
  
  
  METHODS
  The MEDLINE, Embase, and the Cochrane Controlled Trials Register databases were systematically searched, and all included studies were critically appraised by two independent reviewers. The meta-analysis was performed using a random effects model.
  
  
  RESULTS
  Ten studies, totaling 499 patients, were included in this meta-analysis. No significant differences were observed in major amputation rates (relative risk [RR] 0.91; 95% confidence interval [CI] 0.65-1.27), survival (RR 1.00; 95% CI 0.95-1.06), and amputation free survival (RR 1.03; 95% CI 0.86-1.23) between the cell treated and placebo treated patients. The ankle brachial index (mean difference 0.11; 95% CI 0.07-0.16), transcutaneous oxygen measurements (mean difference 11.88; 95% CI 2.73-21.02), and pain score (mean difference -0.72; 95% CI -1.37 to -0.07) were significantly better in the treatment group than in the placebo group.
  
  
  CONCLUSIONS
  This meta-analysis of placebo controlled trials showed no advantage of stem cell therapy on the primary outcome measures of amputation, survival, and amputation free survival in patients with CLI. The potential benefit of more sophisticated cell based strategies should be explored in future randomized placebo controlled trials.
authors.affiliation: Department of Vascular Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584CX, Utrecht, The Netherlands.
authors.forename: S M O
authors.initials: SM
authors.lastname: Peeters Weem
authors.affiliation: Department of Vascular Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584CX, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Teraa
authors.affiliation: Department of Vascular Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584CX, Utrecht, The Netherlands. Electronic address: G.J.deBorst-2@umcutrecht.nl.
authors.forename: G J
authors.initials: GJ
authors.lastname: de Borst
authors.affiliation: Department of Nephrology and Hypertension, University Medical Center Utrecht, Heidelberglaan 100, 3584CX, Utrecht, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Verhaar
authors.affiliation: Department of Vascular Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584CX, Utrecht, The Netherlands.
authors.forename: F L
authors.initials: FL
authors.lastname: Moll
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000671:Amputation, Surgical; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000401:mortality; D016009:Chi-Square Distribution; D016638:Critical Illness; D018572:Disease-Free Survival; D006801:Humans; D007511:Ischemia / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000601:surgery*; D023821:Limb Salvage; D008875:Middle Aged; D016017:Odds Ratio; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000601:surgery*; D016032:Randomized Controlled Trials as Topic; D012086:Reoperation; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
keywords: Bone marrow -derived cell therapy; CLI; Cell therapy; Critical limb ischemia; Meta-analysis; Peripheral arterial disease