Human relevance of pre-clinical studies in stem cell therapy: systematic review and meta-analysis of large animal models of ischaemic heart disease

T.I.G. van der Spoel, S.J. Jansen of Lorkeers, P. Agostoni, E. van Belle, M Gyöngyösi, J.P.G. Sluijter, M.J.M. Cramer, P.A.F.M. Doevendans, S.A.J. Chamuleau

Research output: Contribution to journalLiterature reviewpeer-review

Abstract

Aims Stem cell therapy is a treatment strategy for ischaemic heart disease patients. Meta-analysis of randomized human trials showed

Methods and results Random-effects meta-analysis was performed on pig, dog, or sheep studies investigating the effect of cardiac stem cell therapy in ischaemic cardiomyopathy (52 studies; n = 888 animals). Endpoints were LVEF and death. Ischaemia/reperfusion infarction was performed in 23 studies and chronic occlusion in 29 studies. Pooled analysis showed a LVEF 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 LVEF 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 infarction (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 (= 107), chronic occlusion 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 LVEF. Future trials should focus on cell types other than BM-MNC, large infarction, and strategies to obtain sustained effects.

Original languageEnglish
Pages (from-to)649-658
Number of pages10
JournalCardiovascular Research
Volume91
Issue number4
DOIs
Publication statusPublished - 1 Sept 2011

Keywords

  • Meta-analysis
  • Myocardial infarction
  • Animal models
  • Cell therapy
  • Stem cells
  • ACUTE MYOCARDIAL-INFARCTION
  • LEFT-VENTRICULAR FUNCTION
  • MARROW MONONUCLEAR-CELLS
  • SKELETAL MYOBLAST TRANSPLANTATION
  • RANDOMIZED CONTROLLED-TRIALS
  • BONE-MARROW
  • PORCINE MODEL
  • PROGENITOR CELLS
  • INTRACORONARY DELIVERY
  • CARDIAC-FUNCTION

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