Abstract
Background
Until now there were no clinical studies or systematic reviews to investigate the impact of timing on efficacy and safety of intracoronary bone marrow stem cell (BMSC) transfer in patients with acute myocardial infarction (AMI).
Hypothesis
Timing of BMSC administration might play an important role in the therapeutic response in AMI patients.
Methods
A systematic literature search of PubMed, MEDLINE, and Cochrane Evidence‐Based Medicine (EBM) databases was made on randomized controlled trials with at least 3‐month follow‐up data for patients with AMI undergoing emergent percutaneous coronary intervention (PCI) and receiving intracoronary BMSC transfer thereafter.
Results
A total of 7 trials with 660 patients were available for analysis. Compared to baseline level, BMSC transfer at 4 to 7 days post‐AMI significantly improved left ventricular ejection fraction (LVEF; 4.63% increase, 95% confidence interval [CI]: 1.00%‐8.26%, P = 0.01), reduced left ventricular (LV) end‐systolic dimensions (95% CI: − 0.53 − 0.02, P = 0.03), decreased the incidences of revascularization (odds ratio [OR]: 0.60, 95% CI: 0.37–0.97, P = 0.04), decreased the cumulative clinical events of death or recurrent myocardial infarction (OR: 0.32, 95% CI: 0.11–0.95, P = 0.04), and decreased culprit artery restenosis or ventricular arrhythmia (OR: 0.59, 95% CI: 0.36–0.96, P = 0.03) however these improvements did not reach statistical significance in emergent transfer trials (within 24 hour post‐AMI). Compared with emergent transfer, intracoronary BMSC therapy at 4 to 7 days also significantly reduced the incidence of revascularization (P for interaction = 0.02).
Conclusions
BMSC transfer at 4 to 7 days post‐AMI was superior to that within 24 hours in improving LVEF, decreasing LV end‐systolic dimensions, and reducing the incidence of revascularization. Copyright © 2009 Wiley Periodicals, Inc.
Full Text
The Full Text of this article is available as a PDF (940.8 KB).
References
- 1. Zhang S, Sun A, Ge J, et al. Intracorovnary autologous bone marrow stem cells transfer for patients with acute myocardial infarction: A meta‐analysis of randomised controlled trials. Int J Cardiol http://www.sciencedirect.com/science/article/B6T16‐4T1SK8X‐2/2/adaa2a2b3cee5dd03350bdd5c50429ba. [DOI] [PubMed] [Google Scholar]
- 2. Shantsila E, Watson T, Lip GY. Endothelial progenitor cells in cardiovascular disorders. J Am Coll Cardiol 2007; 49: 741–752. [DOI] [PubMed] [Google Scholar]
- 3. Bartunek J, Wijns W, Heyndrickx GR, Vanderheyden M. Timing of intracoronary bone‐marrow‐derived stem cell transplantation after ST‐elevation myocardial infarction. Nat Clin Pract Cardiovasc Med 2006; 3(suppl 1): S52–56. [DOI] [PubMed] [Google Scholar]
- 4. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials 1996; 17: 1–12. [DOI] [PubMed] [Google Scholar]
- 5. Janssens S, Dubois C, Bogaert J, et al. Autologous bone marrow‐derived stem‐cell transfer in patients with ST‐segment elevation myocardial infarction: double‐blind, randomised controlled trial. Lancet 2006; 367: 113–121. [DOI] [PubMed] [Google Scholar]
- 6. Schachinger V, Erbs S, Elsasser A, et al. Intracoronary bone marrow‐derived progenitor cells in acute myocardial infarction. N Engl J Med 2006; 355: 1210–1221. [DOI] [PubMed] [Google Scholar]
- 7. Schachinger V, Erbs S, Elsasser A, et al. Improved clinical outcome after intracoronary administration of bone‐marrow‐derived progenitor cells in acute myocardial infarction: final 1‐year results of the REPAIR‐AMI trial. Eur Heart J 2006; 27: 2775–2783. [DOI] [PubMed] [Google Scholar]
- 8. Ge J, Li Y, Qian J, et al. Efficacy of emergent transcatheter transplantation of stem cells for treatment of acute myocardial infarction (TCT‐STAMI). Heart 2006; 92: 1764–1767. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Wollert KC, Meyer GP, Lotz J, et al. Intracoronary autologous bone‐marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 2004; 364: 141–148. [DOI] [PubMed] [Google Scholar]
- 10. Meyer GP, Wollert KC, Lotz J, et al. Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months follow‐up data from the randomized, controlled BOOST (bone marrow transfer to enhance ST‐elevation infarct regeneration) trial. Circulation 2006; 113: 1287–1294. [DOI] [PubMed] [Google Scholar]
- 11. Lunde K, Solheim S, Aakhus S, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 2006; 355: 1199–1209. [DOI] [PubMed] [Google Scholar]
- 12. Yao K, Huang RC, Ge L, et al. Observation on the safety: clinical trial on intracoronary autologous bone marrow mononuclear cells transplantation for acute myocardial infarction. Chin J Cardiol 2006; 34: 577–581. [PubMed] [Google Scholar]
- 13. Suarez de Lezo J, Herrera C, Pan M, et al. Regenerative therapy in patients with a revascularized acute anterior myocardial infarction and depressed ventricular function. Rev Esp Cardiol 2007; 60: 357–365. [PubMed] [Google Scholar]
- 14. Deten A, Volz HC, Briest W, Zimmer HG. Cardiac cytokine expression is upregulated in the acute phase after myocardial infarction. Experimental studies in rats. Cardiovas Res 2002; 55: 329–340. [DOI] [PubMed] [Google Scholar]
- 15. Soeki T, Tamura Y, Shinohara H, et al. Serial changes in serum VEGF and HGF in patients with acute myocardial infarction. Cardiology 2000; 93: 168–174. [DOI] [PubMed] [Google Scholar]
- 16. Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone‐marrow‐derived angioblasts prevents cardiomyocyte apoptosis, reduces remod‐ eling and improves cardiac function. Nat Med 2001; 7: 430–436. [DOI] [PubMed] [Google Scholar]
- 17. Mangi AA, Noiseux N, Kong D, et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med 2003; 9: 1195–201. [DOI] [PubMed] [Google Scholar]
- 18. Kawamoto A, Gwon HC, Iwaguro H, et al. Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation 2001; 103: 634–637. [DOI] [PubMed] [Google Scholar]
- 19. Mansour S, Vanderheyden M, De Bruyne B, et al. Intracoronary delivery of hematopoietic bone marrow stem cells and luminal loss of the infarct‐related artery in patients with recent myocardial infarction. J Am Coll Cardiol 2006; 47: 1727–1730. [DOI] [PubMed] [Google Scholar]
- 20. Breitbach M, Bostani T, Roell W, et al. Potential risks of bone marrow cell transplantation into infarcted hearts. Blood 2007; 110: 1362–1369. [DOI] [PubMed] [Google Scholar]
- 21. Kang HJ, Kim HS, Zhang SY, et al. Effects of intracoronary infusion of peripheral blood stem‐cells mobilised with granulocyte‐colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial. Lancet 2004; 363: 751–756. [DOI] [PubMed] [Google Scholar]
- 22. Erbs S, Linke A, Schachinger V, et al. Restoration of microvascular function in the infarct‐related artery by intracoronary transplantation of bone marrow progenitor cells in patients with acute myocardial infarction: the Doppler substudy of the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR‐AMI) trial. Circulation 2007; 116: 366–374. [DOI] [PubMed] [Google Scholar]
- 23. Candipan RC, Wang BY, Buitrago R, Tsao PS, Cooke JP. Regression or progression. Dependency on vascular nitric oxide. Arterioscler Thromb Vasc Biol 1996; 16: 44–50. [DOI] [PubMed] [Google Scholar]