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The efficacy of bone marrow mononuclear stem cell transplantation in patients with non-ischemic dilated cardiomyopathy—a meta analysis

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Abstract

Cardiomyopathy refers to a wide spectrum of heart pathologies that interfere with normal heart function. Management options of patients with cardiomyopathy depended mainly on the severity of the condition. Lifestyle modifications and regular exercise together with a healthy diet is compatible for mild conditions. Severe conditions, however, rely on medications or surgery. Here, we aim to investigate the efficacy of bone marrow mononuclear stem cell transplantation in patients with dilated cardiomyopathy. We searched PubMed, Scopus, and Cochrane CENTRAL for relevant clinical trials and excluded observational studies. We performed the quality assessment of this study following GRADE guidelines. The assessment of the risk of bias was performed by the Cochrane’s risk of bias tool. We present an analysis of the following outcomes: left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and six minutes walking test. Data were pooled as mean differences (MD) and relative confidence intervals (CI). The analysis of 667 patients from 11 studies receiving autologous bone marrow cell therapy for non-ischemic dilated cardiomyopathy is presented. A total of 338 patients were allocated to the treatment group, and 329 participants entered the control group. The mean age of the patients in the treatment group is 52.4 ± 4.3 years, while that of the control is 53.7 ± 3.7 years. Seven studies (14.18–23) reported transplantation through the intracoronary route. Table 1 shows a summary of the baseline characteristics of the included studies and participants, the number of injected cells, and the type of injected cells in each trial. Table 2 summarizes and illustrates the previous treatment history of included patients in each trial, as well as the baseline values of different scores used as outcome measures in this analysis. We found that bone marrow mononuclear stem cell therapy leads to significantly increased LVEF (MD = 4.54%, 95% CI [3.52, 5.56], P < 0.0001). Patients in the transplant group experienced less left ventricular end-diastolic diameter (millimeter) than the control arm (MD = −1.86 mm, 95% CI [−4.01, 0.29], P = 0.09). Additionally, Patients in the transplant group could walk 28.53 m more than the controls (MD = 28.53 m, 95% CI [2.51, 54.55], P = 0.03). Transplantation of bone marrow stem cells yields acceptable results regarding left ventricular ejection fraction and lowers the left ventricular end-diastolic diameter. Additionally, the six minutes walking test is improved in the transplant group.

Table 1 Demographic data about the included participants
Full size table
Table 2 Previous history of treatment and drug intake by the patients
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References

  1. Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, et al (2006) Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Function. Circulation

  2. Chéhab G, Shalak W, Gerbaka B, Saliba Z (2006) Inflammatory heart diseases in childhood: Lebanese epidemiological survey. J Med Liban

  3. Jefferies JL, Towbin JA (2010) Dilated cardiomyopathy. The Lancet

  4. Laflamme MA, Murry CE (2011) Heart regeneration. Nature

  5. Vrtovec B, Poglajen G, Lezaic L, Sever M, Domanovic D, Cernelc P et al (2013) Effects of intracoronary CD34+ stem cell transplantation in nonischemic dilated cardiomyopathy patients: 5-year follow-up. Circ Res 112(1):165–173

    Article  CAS  Google Scholar 

  6. Seth S, Narang R, Bhargava B, Ray R, Mohanty S, Gulati G et al (2006) Percutaneous intracoronary cellular cardiomyoplasty for nonischemic cardiomyopathy: clinical and histopathological results: the first-in-man ABCD (Autologous Bone Marrow Cells in Dilated Cardiomyopathy) Trial. J Am Coll Cardiol

  7. Fischer-Rasokat U, Assmus B, Seeger FH, Honold J, Leistner D, Fichtlscherer S et al (2009) A pilot trial to assess potential effects of selective intracoronary bone marrow-derived progenitor cell infusion in patients with nonischemic dilated cardiomyopathy: final 1-year results of the transplantation of progenitor cells and functional regenerat. Circ Hear Fail

  8. Ishida M, Tomita S, Nakatani T, Fukuhara S, Hamamoto M, Nagaya N et al (2004) Bone marrow mononuclear cell transplantation had beneficial effects on doxorubicin-induced cardiomyopathy. J Hear Lung Transplant

  9. Hofmann M, Wollert KC, Meyer GP, Menke A, Arseniev L, Hertenstein B et al (2005) Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation

  10. Sant’Anna RT, Kalil RAK, Pretto Neto AS, Pivatto F, Fracasso J, Sant’Anna JRM et al (2010) Global contractility increment in nonischemic dilated cardiomyopathy after free wall-only intramyocardial injection of autologous bone marrow mononuclear cells: an insight over stem cells clinical mechanism of action. Cell Transplant

  11. Moher D, Liberati A, Tetzlaff J, Altman DG, Altman D, Antes G et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Medicine

  12. Higgins JPT, Green S (2008) Cochrane handbook for systematic reviews of interventions: Cochrane book series. Vol. Version 5. 1 p

  13. Bartolucci J, Verdugo FJ, Carrion F, Abarzúa E, Goset C, Lamich R et al (2015) Long-term results of intracoronary transplantation of autologous bone marrow cells in dilated cardiomyopathy. Rev Med Chil 143(4):415–423

    Article  Google Scholar 

  14. Green S, Higgins P. Julian T, Alderson P, Clarke M, Mulrow DC, Oxman DA (2003) Cochrane handbook: Cochrane reviews: ch 8: assessing risk of bias in included studies. In: Cochrane handbook for: systematic reviews of interventions. p. 3–10

  15. RevMan 5 | Cochrane Community [Internet]. [cited 2020 Feb 9]. Available from: https://community.cochrane.org/help/tools-and-software/revman-5

  16. Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. British Medical Journal

  17. Bocchi EA, Bacal F, Guimarães G, Mendroni A, Mocelin A, Filho AE et al (2010) Granulocyte-colony stimulating factor or granulocyte-colony stimulating factor associated to stem cell intracoronary infusion effects in non ischemic refractory heart failure. Int J Cardiol [Internet] 138(1):94–7. Available from: https://doi.org/10.1016/j.ijcard.2008.06.002

  18. Hamshere S, Arnous S, Choudhury T, Choudry F, Mozid A, Yeo C et al (2015) Randomized trial of combination cytokine and adult autologous bone marrow progenitor cell administration in patients with non-ischaemic dilated cardiomyopathy: the REGENERATEDCM clinical trial. Eur Heart J 36(44):3061–3069

    Article  CAS  Google Scholar 

  19. Martino H, Brofman P, Greco O, Bueno R, Bodanese L, Clausell N et al (2015) Multicentre, randomized, double-blind trial of intracoronary autologous mononuclear bone marrow cell injection in non-ischaemic dilated cardiomyopathy (the dilated cardiomyopathy arm of the MiHeart study). Eur Heart J 36(42):2898–2904

    Article  Google Scholar 

  20. Vrtovec B, Poglajen G, Lezaic L, Sever M, Socan A, Domanovic D et al (2013) Comparison of transendocardial and intracoronary CD34+ cell transplantation in patients with nonischemic dilated cardiomyopathy. Circulation 128(1):42–50

    Article  Google Scholar 

  21. Vrtovec B, Poglajen G, Sever M, Lezaic L, Domanovic D, Cernelc P et al (2011) Effects of intracoronary stem cell transplantation in patients with dilated cardiomyopathy. J Card Fail 17(4):272–281

    Article  Google Scholar 

  22. Xiao W, Guo S, Gao C, Dai G, Gao Y, Li M et al (2017) A randomized comparative study on the efficacy of intracoronary infusion of autologous bone marrow mononuclear cells and mesenchymal stem cells in patients with dilated cardiomyopathy. Int Heart J 58(2):238–244

    Article  CAS  Google Scholar 

  23. Frljak S, Jaklic M, Zemljic G, Cerar A, Poglajen G, Vrtovec B (2018) CD34+ cell transplantation improves right ventricular function in patients with nonischemic dilated cardiomyopathy. Stem Cells Transl Med 7(2):168–172

    Article  CAS  Google Scholar 

  24. Hu S, Liu S, Zheng Z, Yuan X, Li L, Lu M et al (2011) Isolated coronary artery bypass graft combined with bone marrow mononuclear cells delivered through a graft vessel for patients with previous myocardial infarction and chronic heart failure: a single-center, randomized, double-blind, placebo-controlled cl. J Am Coll Cardiol 57(24):2409–2415

    Article  Google Scholar 

  25. Seth S, Bhargava B, Narang R, Ray R, Mohanty S, Gulati G et al (2010) The ABCD (Autologous Bone Marrow Cells in Dilated Cardiomyopathy) trial. A long-term follow-up study. J Am Coll Cardiol 55(15):1643–1644. https://doi.org/10.1016/j.jacc.2009.11.070

    Article  PubMed  Google Scholar 

  26. Sant’Anna RT, Fracasso J, Valle FH, Castro I, Nardi NB, Sant’Anna JRM et al (2014) Ensaio clínico prospectivo randomizado sobre terapia com células mononucleares da medula óssea para cardiomiopatia dilatada idiopática: INTRACELL. Brazilian J Cardiovasc Surg 29(3):437–447

    Google Scholar 

  27. Marquis-Gravel G, Stevens LM, Mansour S, Avram R (2014) Noiseuxx 2014 Stem cell therapy for the treatment of nonischemic cardiomyopathy: a systematic review of the literature and meta-analysis of randomized controlled trials. Can J Cardiol 30(11):1378–1384. https://doi.org/10.1016/j.cjca.2014.03.026

    Article  PubMed  Google Scholar 

  28. Wen Y, Ding J, Zhang B, Gao Q (2018) Bone marrow-derived mononuclear cell therapy for nonischaemic dilated cardiomyopathy—a meta-analysis. Eur J Clin Invest

  29. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B et al (2001) Bone marrow cells regenerate infarcted myocardium. Nature

  30. Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F et al (2001) Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA

  31. Joggerst SJ, Hatzopoulos AK (2009) Stem cell therapy for cardiac repair: benefits and barriers. Expert Rev Mol Med

  32. Terrovitis JV, Smith RR, Marbán E (2010) Assessment and optimization of cell engraftment after transplantation into the heart. Circ Res

  33. Penn MS, Mayorga ME (2010) Editorial: Searching for understanding with the cellular lining of life. Circ Res

  34. Seeger FH, Tonn T, Krzossok N, Zeiher AM, Dimmeler S (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

  35. Assmus B, Tonn T, Seeger FH, Yoon CH, Leistner D, Klotsche J et al (2010) Red blood cell contamination of the final cell product impairs the efficacy of autologous bone marrow mononuclear cell therapy. J Am Coll Cardiol

  36. Seeger FH, Rasper T, Fischer A, Muhly-Reinholz M, Hergenreider E, Leistner DM et al (2012) Heparin disrupts the CXCR4/SDF-1 axis and impairs the functional capacity of bone marrow-derived mononuclear cells used for cardiovascular repair. Circ Res

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Authors and Affiliations

  1. Department of Medicine, Icahn School of Medicine At Mount Sinai (Queens Hospital Center), Queens, 17004 Henley Rd Unit 4B, NY, 11432, Jamaica, USA

    Nso Nso

  2. Division of Cardiovascular Disease, University of Chicago (Northshore Program), IL, Evanston, USA

    Kaveh Rezaei Bookani & Robert Gordon

  3. Department of Cardiovascular Disease, SUNY Downstate Health Science University, NY, 11203, Brooklyn, USA

    Sostanie Takota Enoru

  4. Division of Cardiology, Department of Medicine, Icahn School of Medicine At Mount Sinai/Queens (Queens Hospital Center), Jamaica, NY, USA

    Farshid Radparvar

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Contributions

NN conceived the study hypothesis. NN and KRB designed the study and performed the systematic search, study selection, and data extraction. NN analyzed the data. All authors contributed to the interpretation of the data, writing, and critical editing of the manuscript.

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Correspondence to Nso Nso.

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Nso, N., Bookani, K.R., Enoru, S.T. et al. The efficacy of bone marrow mononuclear stem cell transplantation in patients with non-ischemic dilated cardiomyopathy—a meta analysis. Heart Fail Rev 27, 811–820 (2022). https://doi.org/10.1007/s10741-021-10082-0

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