Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.4)
Index Copernicus  – 161.11; MEiN – 140 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 1, January, p. 21–37

doi: 10.17219/acem/66385

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Methodological exploration of bone marrow stem cell therapy in acute myocardial infarction – how to achieve greater benefit on cardiac outcomes: A systematic review and meta-analysis

Mei Yang1,A,B,C,D,E,F, Quanfu Xu1,A,B,C,D,E,F, Bo Liu1,B,C,E, Xiu Chen1,B,C, Yigang Li1,A,E,F

1 Department of Cardiology, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China

Abstract

Background. Clinical trials of intracoronary injection of bone marrow-derived stem cells (BMCs) in patients with acute myocardial infarction (AMI) have revealed promising but variable and modest results. One of the reasons underlying this situation may be the unstandardized preparation of BMCs.
Objectives. The aim of this study was to explore whether methodological differences affect the prognosis of acute myocardial infarction patients who received BMCs transplantation.
Material and Methods. MEDLINE was searched for randomized controlled trials providing AMI patients with intracoronary BMCs injection or a standard therapy. Changes in cardiac parameters and clinical outcomes were analyzed. Subgroup analyses were conducted according to different methodologies for cell preparation, including supplement for serum or plasma, use of heparin and cell washout.
Results. Non-use of serum or plasma in the cell suspension is associated with more reduction in infarct size (IS) and a lower risk of all-cause mortality. Heparin usage could diminish the benefit in reducing IS. All-cause mortality rose significantly without the cell washout procedure when heparin was used.
Conclusion. Methodological differences in BMCs preparation as well as the use of heparin and serum/ plasma impact on the prognosis of AMI patients.

Key words

acute myocardial infarction, bone marrow-derived stem cells transplantation, cell preparation, serum or plasma, heparin

References (37)

  1. Juni P, Altman DG, Egger M. Systematic reviews in health care: Assessing the quality of controlled clinical trials. BMJ. 2001;323:42–46.
  2. Wang X, Xi WC, Wang F. The beneficial effects of intracoronary autologous bone marrow stem cell transfer as an adjunct to percutaneous coronary intervention in patients with acute myocardial infarction. Biotechnol Lett. 2014;36:2163–2168.
  3. 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.
  4. Beitnes JO, Hopp E, Lunde K, et al. Long-term results after intracoronary injection of autologous mononuclear bone marrow cells in acute myocardial infarction: The ASTAMI randomised, controlled study. Heart. 2009;95:1983–1989.
  5. Quyyumi AA, Waller EK, Murrow J. CD34(+) cell infusion after ST elevation myocardial infarction is associated with improved perfusion and is dose dependent. Am Heart J. 2011;161:98–105.
  6. Srimahachota S, Boonyaratavej S, Rerkpattanapipat P, et al. Intra-coronary bone marrow mononuclear cell transplantation in patients with ST-elevation myocardial infarction: A randomized controlled study. J Med Assoc Thai. 2011;94:657–663.
  7. Sürder D, Manka R, Lo Cicero V, et al. Intracoronary injection of bone marrow-derived mononuclear cells early or late after acute myocardial infarction: Effects on global left ventricular function. Circulation. 2013;127:1968–1979.
  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.
  9. Lipiec P, Krzemińska-Pakuła M, Plewka M, et al. Impact of intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction on left ventricular perfusion and function: A 6-month follow-up gated 99mTc-MIBI single-photon emission computed tomography study. Eur J Nucl Med Mol Imaging. 2009;36:587–593.
  10. Cao F, Sun D, Li C, et al. Long-term myocardial functional improvement after autologous bone marrow mononuclear cells transplantation in patients with ST-segment elevation myocardial infarction: 4-year follow-up. Eur Heart J. 2009;30:1986–1994.
  11. Wöhrle J, Merkle N, Mailänder V, et al. Results of intracoronary stem cell therapy after acute myocardial infarction. Am J Cardiol. 2010;105:804–812.
  12. Roncalli J, Mouquet F, Piot C, et al. Intracoronary autologous mononucleated bone marrow cell infusion for acute myocardial infarction: Results of the randomized multicenter BONAMI trial. Eur Heart J. 2011;32:1748–1757.
  13. San Roman JA, Sánchez PL, Villa A, et al.; Comparison of different bone marrow-derived stem cell approaches in reperfused STEMI: A multicenter, prospective, randomized, open-labeled TECAM trial. J Am Coll Cardiol. 2015;65:2372–2382.
  14. Schächinger V, Erbs S, Elsässer A, et al. REPAIR-AMI Investigators. 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.
  15. 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.
  16. Huikuri HV, Kervinen K, Niemelä M, et al.; FINCELL Investigators. Effects of intracoronary injection of mononuclear bone marrow cells on left ventricular function, arrhythmia risk profile, and restenosis after thrombolytic therapy of acute myocardial infarction. Eur Heart J. 2008;29:2723–2732.
  17. Grajek S, Popiel M, Gil L, et al. Influence of bone marrow stem cells on left ventricle perfusion and ejection fraction in patients with acute myocardial infarction of anterior wall: Randomized clinical trial. Impact of bone marrow stem cell intracoronary infusion on improvement of microcirculation. Eur Heart J. 2010;31:691–702.
  18. 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.
  19. 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.
  20. Meyer GP, Wollert KC, Lotz J, et al. Intracoronary bone marrow cell transfer after myocardial infarction: 5-year follow-up from the randomized-controlled BOOST trial. Eur Heart J. 2009;30:2978–2984.
  21. Plewka M, Krzemińska-Pakuła M, Lipiec P, et al. Effect of intracoronary injection of mononuclear bone marrow stem cells on left ventricular function in patients with acute myocardial infarction. Am J Cardiol. 2009;104:1336–1342.
  22. Nogueira FB, Silva SA, Haddad AF, et al. Systolic function of patients with myocardial infarction undergoing autologous bone marrow transplantation. Arq Bras Cardiol. 2009;93:367–372.
  23. Silva SA, Sousa AL, Haddad AF, et al. Autologous bone-marrow mononuclear cell transplantation after acute myocardial infarction: Comparison of two delivery techniques. Cell Transplant. 2009;18:343–352.
  24. Traverse JH, McKenna DH, Harvey K, et al. Results of a phase 1, randomized, double-blind, placebo-controlled trial of bone marrow mononuclear stem cell administration in patients following ST-elevation myocardial infarction. Am Heart J. 2010;160:428–434.
  25. Colombo A, Castellani M, Piccaluga E, et al. Myocardial blood flow and infarct size after CD133+ cell injection in large myocardial infarction with good recanalization and poor reperfusion: Results from a randomized controlled trial. J Cardiovasc Med (Hagerstown). 2011;12:239–248.
  26. Hirsch A, Nijveldt R, van der Vleuten PA, et al.; HEBE Investigators. Intracoronary infusion of mononuclear cells from bone marrow or peripheral blood compared with standard therapy in patients after acute myocardial infarction treated by primary percutaneous coronary intervention: Results of the randomized controlled HEBE trial. Eur Heart J. 2011;32:1736–1747.
  27. Delewi R, van der Laan AM, Robbers LF, et al.; HEBE investigators. Long term outcome after mononuclear bone marrow or peripheral blood cells infusion after myocardial infarction. Heart. 2015;101:363–368.
  28. Traverse JH, Henry TD, Ellis SG, et al. Cardiovascular Cell Therapy ResearchNetwork: Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: The late TIME randomized trial. JAMA. 2011;306:2110–2119.
  29. Traverse JH, Henry TD, Pepine CJ, et al.; Cardiovascular Cell Therapy Research Network (CCTRN). Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute myocardial infarction: The TIME randomized trial. JAMA. 2012;308:2380–2389.
  30. Traverse JH, Henry TD, Pepine CJ, Willerson JT, Ellis SG. One-year follow-up of intracoronary stem cell delivery on left ventricular function following ST-elevation myocardial infarction. JAMA. 2014;311:301–302.
  31. De Jong R, Houtgraaf JH, Samiei S, Boersma E, Duckers HJ. Intracoronary stem cell infusion after acute myocardial infarction: A meta-analysis and update on clinical trials. Circ Cardiovasc Interv. 2014;7:156–167.
  32. Xu Q, Seeger FH, Castillo J, et al. Micro-RNA-34a contributes to the impaired function of bone marrow-derived mononuclear cells from patients with cardiovascular disease. J Am Coll Cardiol. 2012;59:2107–2117.
  33. Seeger FH, Tonn T, Krzossok N, Zeiher AM, Dimmeler S. Cell isolation procedures matter: A comparison of different isolation protocols of bone marrow mononuclear cells used for cell therapy in patients with acute myocardial infarction. Eur Heart J. 2007;28:766–772.
  34. Assmus B, Walter DH, Seeger FH, et al. Effect of shock wave-facilitated intracoronary cell therapy on LVEF in patients with chronic heart failure: The CELLWAVE randomized clinical trial. JAMA. 2013;309:1622–1631.
  35. Seeger FH, Rasper T, Bönig H, Assmus B, Zeiher AM, Dimmeler S. The challenges of autologous cell therapy: Systemic anti-thrombotic therapies interfering with serum coagulation may disable autologous serum-containing cell products for therapeutical use. J Cardiovasc Transl Res. 2014;7:644–650.
  36. Seeger FH, Rasper T, Fischer A, et al. Heparin disrupts the cxcr4/sdf-1 axis and impairs the functional capacity of bone marrow-derived mononuclear cells used for cardiovascular repair. Circ Res. 2012;111:854–862.
  37. Jeevanantham V, Butler M, Saad A, Abdel-Latif A, Zuba-Surma EK, Dawn B. Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters: A systematic review and meta-analysis. Circulation. 2012;126:551–568.
© Wroclaw Medical University