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Randomized, controlled trial of intramuscular or intracoronary injection of autologous bone marrow cells into scarred myocardium during CABG versus CABG alone

Nature Clinical Practice Cardiovascular Medicine volume 5, pages 663–670 (2008)Cite this article

Abstract

Background Studies of the transplantation of autologous bone marrow cells (BMCs) in patients with chronic ischemic heart disease have assessed effects on viable, peri-infarct tissue. We conducted a single-blinded, randomized, controlled study to investigate whether intramuscular or intracoronary administration of BMCs into nonviable scarred myocardium during CABG improves contractile function of scar segments compared with CABG alone.

Methods Elective CABG patients (n = 63), with established myocardial scars diagnosed as akinetic or dyskinetic segments by dobutamine stress echocardiography and confirmed at surgery, were randomly assigned CABG alone (control) or CABG with intramuscular or intracoronary administration of BMCs. The BMCs, which were obtained at the time of surgery, were injected into the mid-depth of the scar in the intramuscular group or via the graft conduit supplying the scar in the intracoronary group. Contractile function was assessed in scar segments by dobutamine stress echocardiography before and 6 months after treatment.

Results The proportion of patients showing improved wall motion in at least one scar segment after BMC treatment was not different to that observed in the control group (P = 0.092). Quantitatively, systolic fractional thickening in scar segments did not improve with BMC administration. Furthermore, BMCs did not improve scar transmurality, infarct volume, left ventricular volume, or ejection fraction.

Conclusion Injection of autologous BMCs directly into the scar or into the artery supplying the scar is safe but does not improve contractility of nonviable scarred myocardium, reduce scar size, or improve left ventricular function more than CABG alone.

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References

  1. Tomita S et al. (1999) Autologous transplantation of bone marrow cells improves damaged heart function. Circulation 100: II247–II256

    Article  CAS  Google Scholar 

  2. Orlic D et al. (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410: 701–705

    Article  CAS  Google Scholar 

  3. Patel AN et al. (2005) Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: a prospective randomized study. J Thorac Cardiovasc Surg 130: 1631–1638

    Article  Google Scholar 

  4. Hendrikx M et al. (2006) Recovery of regional but not global contractile function by the direct intramyocardial autologous bone marrow transplantation: results from a randomized controlled clinical trial. Circulation 114: I101–107

    Article  Google Scholar 

  5. Stamm C et al. (2007) Intramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafting for chronic ischemic heart disease: safety and efficacy studies. J Thorac Cardiovasc Surg 133: 717–725

    Article  Google Scholar 

  6. Galiñanes M et al. (2004) Autotransplantation of unmanipulated bone marrow into scarred myocardium is safe and enhances cardiac function in humans. Cell Transplant 13: 7–13

    Article  Google Scholar 

  7. Nagueh SF et al. (1999) Relation of the contractile reserve of hibernating myocardium to myocardial structure in humans. Circulation 100: 490–496

    Article  CAS  Google Scholar 

  8. Kim RJ et al. (1999) Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation 100: 1992–2002

    Article  CAS  Google Scholar 

  9. Grothues F et al. (2002) Comparison of interstudy reproducibility of cardiovascular magnetic resonance with two-dimensional echocardiography in normal subjects and in patients with heart failure or left ventricular hypertrophy. Am J Cardiol 90: 29–34

    Article  Google Scholar 

  10. Zhang H et al. (2007) Injection of bone marrow mesenchymal stem cells in the borderline area of infarcted myocardium: heart status and cell distribution. J Thorac Cardiovasc Surg 134: 1234–1240

    Article  CAS  Google Scholar 

  11. Schiller NB et al. (1989) Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 2: 358–367

    Article  CAS  Google Scholar 

  12. Hoffmann R et al. (1996) Analysis of interinstitutional observer agreement in interpretation of dobutamine stress echocardiograms. J Am Coll Cardiol 27: 330–336

    Article  CAS  Google Scholar 

  13. Hoffmann R et al. (2002) Refinements in stress echocardiographic techniques improve inter-institutional agreement in interpretation of dobutamine stress echocardiograms. Eur Heart J 23: 821–829

    Article  CAS  Google Scholar 

  14. MASS analysis (Medis, Leiden, Netherlands)

  15. Guyatt GH et al. (1987) A controlled trial of ambroxol in chronic bronchitis. Chest 92: 618–620

    Article  CAS  Google Scholar 

  16. SPSS version 14® (SPSS Inc., Chicago, IL, USA

  17. SAS version 9.1 (SAS® Institute Inc., Cary, IN, USA)

  18. Seeger FH et al. (2007) 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 28: 766–772

    Article  Google Scholar 

  19. Shi Q et al. (1998) Evidence for circulating bone marrow-derived endothelial cells. Blood 92: 362–367

    CAS  PubMed  Google Scholar 

  20. Quirici N et al. (2001) Differentiation and expansion of endothelial cells from human bone marrow CD133+ cells. Br J Haematol 115: 186–194

    Article  CAS  Google Scholar 

  21. Asahara T et al. (1999) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85: 221–228

    Article  CAS  Google Scholar 

  22. Balsam LB et al. (2004) Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 428: 668–673

    Article  CAS  Google Scholar 

  23. Murry CE et al. (2004) Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 428: 664–668

    Article  CAS  Google Scholar 

  24. Kocher AA et al. (2001) Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 7: 430–436

    Article  CAS  Google Scholar 

  25. Schuster MD et al. (2004) Myocardial neovascularization by bone marrow angioblasts results in cardiomyocyte regeneration. Am J Physiol Heart Circ Physiol 287: H525–H532

    Article  CAS  Google Scholar 

  26. Ziegelhoeffer T et al. (2004) Bone marrow-derived cells do not incorporate into the adult growing vasculature. Circ Res 94: 230–238

    Article  CAS  Google Scholar 

  27. Fukushima S et al. (2007) Direct intramyocardial but not intracoronary injection of bone marrow cells induces ventricular arrhythmias in a rat chronic ischemic heart failure model. Circulation 115: 2254–2261

    Article  Google Scholar 

  28. Menasche P et al. (2008) The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation 117: 1189–1200

    Article  Google Scholar 

  29. Hamano K et al. (2001) Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease: clinical trial and preliminary results. Jpn Circ J 65: 845–847

    Article  CAS  Google Scholar 

  30. Strauer BE et al. (2002) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106: 1913–1918

    Article  Google Scholar 

  31. Perin EC et al. (2003) Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 107: 2294–2302

    Article  Google Scholar 

  32. Assmus B et al. (2002) Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation 106: 3009–3017

    Article  Google Scholar 

  33. Menasche P et al. (2003) Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol 41: 1078–1083

    Article  Google Scholar 

Download references

Acknowledgements

We thank W Rathbone and E McGlynn for their technical assistance and N Harris, A Vickers, L Middleton and S Garbett for their help. We also thank A Mathur for his valuable comments. This study was funded by the British Heart Foundation (grant PG04050).

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Authors and Affiliations

  1. Department of Cardiovascular Science, Cardiac Surgery Unit, University of Leicester, UK

    Keng-Leong Ang, Chandrashekhar Kubal, Lakshmi Srinivasan, Lizelle Bernhardt, Lincoln T Shenje & Manuel Galiñanes

  2. Department of Cardiology, Glenfield Hospital, Leicester, UK

    Derek Chin

  3. Department of Cardiology, University of Birmingham, Good Hope Hospital, Sutton Coldfield, Birmingham, UK

    Francisco Leyva, Paul Foley & Shajil Chalil

  4. Department of Cardiovascular Science, Medical Statistician, University of Leicester, UK

    Suzanne Stevens

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Correspondence to Manuel Galiñanes.

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Ang, KL., Chin, D., Leyva, F. et al. Randomized, controlled trial of intramuscular or intracoronary injection of autologous bone marrow cells into scarred myocardium during CABG versus CABG alone. Nat Rev Cardiol 5, 663–670 (2008). https://doi.org/10.1038/ncpcardio1321

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