XXXX relevance of pre-clinical studies in stem cell therapy: systematic review and meta-analysis of large animal models of @entity299 .

@entity1 @entity1707 @entity296 @entity742 @entity235 @entity1188 @entity299 @entity432 @entity204 @entity1002
AIMS: Stem cell therapy is a treatment strategy for @entity299 @entity1 . Meta-analysis of randomized @entity1 trials showed <5% improvement in @entity1002 ( @entity1002 ). Meta-analysis of available pre-clinical data of @entity299 could provide important clues to design @entity1 clinical trials. METHODS AND RESULTS: Random-effects meta-analysis was performed on @entity1707 , @entity235 , or @entity742 studies investigating the effect of cardiac stem cell therapy in @entity296 (52 studies; n = 888 animals). Endpoints were @entity1002 and @entity204 . Ischaemia/reperfusion @entity1188 was performed in 23 studies and @entity432 in 29 studies. Pooled analysis showed a @entity1002 difference of 7.5% at follow-up after cell therapy vs. control (95% confidence interval, 6.2-8.9%; P < 0.001). By exploratory multivariable meta-regression, significant predictors of @entity1002 improvement were: cell type [bone marrow mononuclear cells (BM-MNC) showed less effect than other cell types, e.g. mesenchymal stem cells; P = 0.040] and type of @entity1188 (left anterior descending artery 8.0 vs. left circumflex artery 5.8%; P = 0.045). Cell therapy was not associated with increased mortality (P = 0.68). Sensitivity analysis showed trends towards more improvement with higher cell number (>= 10(7)), @entity432 models, and late injections (>1 week). After follow-up of 8 weeks, the effect of cell therapy decreased to 6%. CONCLUSION: This meta-analysis showed that large animal models are valid to predict the outcome of clinical trials. Our results showed that cell therapy is safe and leads to a preserved @entity1002 . Future trials should focus on cell types other than BM-MNC, large @entity1188 , and strategies to obtain sustained effects.
