title: Stem cell treatment for acute myocardial infarction.
abstract: BACKGROUND
  Stem cell therapy offers a promising approach to the regeneration of damaged vascular and cardiac tissue after acute myocardial infarction (AMI). This has resulted in multiple randomised controlled trials (RCTs) worldwide.
  
  
  OBJECTIVE
  To critically evaluate evidence from RCTs on the effectiveness of adult bone marrow-derived stem cells (BMSC) to treat acute myocardial infarction (AMI).
  
  
  METHODS
  This Cochrane review is an update of a previous one (published in 2008). MEDLINE (1950 to January 2011), EMBASE (1974 to January 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1, 2011), CINAHL (1982 to January 2011) and the Transfusion Evidence Library (1980 to January 2011) were searched. In addition, several international and ongoing trial databases were searched and handsearching of relevant conference proceedings undertaken to January 2011.
  
  
  METHODS
  RCTs comparing autologous stem/progenitor cells with no autologous stem/progenitor cells in patients diagnosed with AMI were eligible.
  
  
  METHODS
  Two authors independently screened all references, assessed trial quality and extracted data. Meta-analyses using a random-effects model were conducted and heterogeneity was explored for the primary outcome using sub-group analyses.
  
  
  RESULTS
  Thirty-three RCTs (1765 participants) were eligible for inclusion. Stem/progenitor cell treatment was not associated with statistically significant changes in the incidence of mortality (RR 0.70, 95% CI 0.40 to 1.21) or morbidity (the latter measured by re-infarction, hospital re-admission, restenosis and target vessel revascularisation). A considerably high degree of heterogeneity has been observed among the included trials. In short-term follow up, stem cell treatment was observed to improve left ventricular ejection fraction (LVEF) significantly (WMD 2.87, 95% CI 2.00 to 3.73). This improvement in LVEF was maintained over long-term follow up of 12 to 61 months (WMD 3.75, 95% CI 2.57 to 4.93). With certain measurements and at certain times, stem cell treatment was observed to reduce left ventricular end systolic and end diastolic volumes (LVESV & LVEDV) and infarct size significantly in long-term follow up. There was a positive correlation between mononuclear cell dose infused and the effect on LVEF measured by magnetic resonance imaging. A correlation between timing of stem cell treatment and effect on LVEF measured by left ventricular angiography was also observed.
  
  
  CONCLUSIONS
  Despite the high degree of heterogeneity observed, the results of this systematic review suggest that moderate improvement in global heart function is significant and sustained long-term. However, because mortality rates after successful revascularization of the culprit arteries are very low, larger number of participants would be required to assess the full clinical effect of this treatment. Standardisation of methodology, cell dosing and cell product formulation, timing of cell transplantation and patient selection may also be required in order to reduce the substantial heterogeneity observed among the included studies.
authors.affiliation: StemCell Research Lab, NuffieldDepartment of ClinicalLaboratory Sciences, University of Oxford, Oxford, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Clifford
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Fisher
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Brunskill
authors.forename: Carolyn
authors.initials: C
authors.lastname: Doree
authors.forename: Anthony
authors.initials: A
authors.lastname: Mathur
authors.forename: Suzanne
authors.initials: S
authors.lastname: Watt
authors.forename: Enca
authors.initials: E
authors.lastname: Martin-Rendon
mesh_terms: D006801:Humans; D009203:Myocardial Infarction / Q000401:mortality / Q000601:surgery*; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D013318:Stroke Volume / Q000502:physiology