Long-term effects of autologous bone marrow stem cell treatment in acute myocardial infarction: factors that may influence outcomes.
OBJECTIVE
To investigate whether there are important sources of heterogeneity between the findings of different clinical trials which administer autologous stem cell treatment for acute myocardial infarction (AMI) and to evaluate what factors may influence the long-term effects of this treatment.


RESULTS
MEDLINE (1950-January 2011), EMBASE (1974-January 2011), CENTRAL (The Cochrane Library 2011, Issue 1), CINAHL (1982-January 2011), and ongoing trials registers were searched for randomised trials of bone marrow stem cells as treatment for AMI. Hand-searching was used to screen recent, relevant conference proceedings (2005-2010/11). Meta-analyses were conducted using random-effects models and heterogeneity between subgroups was assessed using chi-squared tests. Planned analyses included length of follow-up, timing of cell infusion and dose, patient selection, small trial size effect, methodological quality, loss of follow-up and date of publication. Thirty-three trials with a total of 1,765 participants were included. There was no evidence of bias due to publication or time-lag, methodological quality of included studies, participant drop-out, duration of follow-up or date of the first disclosure of results. However, in long-term follow-ups the treatment seemed more effective when administered at doses greater than 10(8) cells and to patients with more severe heart dysfunction.


CONCLUSIONS
Evaluation of heterogeneity between trials has not identified significant sources of bias in this study. However, clinical differences between trials are likely to exist which should be considered when undertaking future trials.
Stem Cell Research Laboratory, NHS-Blood and Transplant, John Radcliffe Hospital, Oxford, United Kingdom.
David M
DM
Clifford
Sheila A
SA
Fisher
Susan J
SJ
Brunskill
Carolyn
C
Doree
Anthony
A
Mathur
Mike J
MJ
Clarke
Suzanne M
SM
Watt
Enca
E
Martin-Rendon
D000208:Acute Disease; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D009203:Myocardial Infarction / Q000601:surgery*; D013995:Time; D014182:Transplantation, Autologous; D016896:Treatment Outcome