Skip to main content

Bone Marrow Cell Therapy for Ischemic Heart Disease and the Role of Cardiac Imaging in Evaluation of Outcomes

  • Chapter
  • First Online:
Imaging in Stem Cell Transplant and Cell-based Therapy

Abstract

Cell therapy for cardiac repair has gained vigorous momentum over the past two decades. Several different types of cells, including skeletal myoblasts, cardiac stem cells, and bone marrow cells (BMCs) have been used in patients with myocardial infarction and cardiomyopathy. A large number of clinical trials of BMC therapy that each enrolled a small number of patients have already been completed. Although results from these trials utilizing diverse cell types injected via different routes in greatly variable numbers have been disparate, findings from the majority of meta-analyses indicate that BMC therapy is beneficial. These results show a modest yet significant improvement in cardiac structural and functional parameters in BMC-treated patients compared with controls. Importantly, subgroup analysis of pooled data shows generally concordant findings with regard to changes in LV structure and function measured by left ventriculogram, echocardiography, SPECT and MRI. However, the selection of imaging technique(s) for cell therapy trials often depends on not only accuracy of data, but also logistics and patient characteristics. Furthermore, besides information gathered by imaging, the effects of cell therapy are also reflected in patient outcomes. Cumulative evidence from meta-analyses also indicates that BMC therapy is associated with improvement in patient survival and other important clinical end-points. The outcomes from ongoing large randomized controlled trials are eagerly awaited at this time for conclusive answers in an emerging and highly promising field.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Gibson CM, Pride YB, Frederick PD, Pollack Jr CV, Canto JG, Tiefenbrunn AJ, Weaver WD, Lambrew CT, French WJ, Peterson ED, Rogers WJ. Trends in reperfusion strategies, door-to-needle and door-to-balloon times, and in-hospital mortality among patients with st-segment elevation myocardial infarction enrolled in the national registry of myocardial infarction from 1990 to 2006. Am Heart J. 2008;156:1035–44.

    Article  PubMed  Google Scholar 

  2. Pfeffer MA, Braunwald E, Moyé LA, Basta L, Brown EJ, Cuddy TE, Davis BR, Geltman EM, Goldman S, Flaker GC, Klein M, Lamas GA, Packer M, Rouleau J, Rouleau JL, Rutherford J, Wertheimer JH, Hawkins CM. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 1992;327:669–77.

    Article  CAS  PubMed  Google Scholar 

  3. Foody JM, Shah R, Galusha D, Masoudi FA, Havranek EP, Krumholz HM. Statins and mortality among elderly patients hospitalized with heart failure. Circulation. 2006;113:1086–92.

    Article  CAS  PubMed  Google Scholar 

  4. Marelli D, Desrosiers C. el-Alfy M, Kao RL, Chiu RC. Cell transplantation for myocardial repair: an experimental approach. Cell Transplant. 1992;1:383–90.

    CAS  PubMed  Google Scholar 

  5. Van Meter Jr CH, Claycomb WC, Delcarpio JB, Smith DM, DeGruiter H, Smart F, Ochsner JL. Myoblast transplantation in the porcine model: a potential technique for myocardial repair. J Thorac Cardiovasc Surg. 1995;110:1442–8.

    Article  PubMed  Google Scholar 

  6. Klug MG, Soonpaa MH, Koh GY, Field LJ. Genetically selected cardiomyocytes from differentiating embronic stem cells form stable intracardiac grafts. J Clin Invest. 1996;98:216–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Taylor DA, Silvestry SC, Bishop SP, Annex BH, Lilly RE, Glower DD, Kraus WE. Delivery of primary autologous skeletal myoblasts into rabbit heart by coronary infusion: a potential approach to myocardial repair. Proc Assoc Am Physicians. 1997;109:245–53.

    CAS  PubMed  Google Scholar 

  8. Kocher AA, Schuster MD, Szabolcs MJ, Takuma S, Burkhoff D, Wang J, Homma S, Edwards NM, Itescu S. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med. 2001;7:430–6.

    Article  CAS  PubMed  Google Scholar 

  9. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P. Bone marrow cells regenerate infarcted myocardium. Nature. 2001;410:701–5.

    Article  CAS  PubMed  Google Scholar 

  10. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, Kasahara H, Rota M, Musso E, Urbanek K, Leri A, Kajstura J, Nadal-Ginard B, Anversa P. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003;114:763–76.

    Article  CAS  PubMed  Google Scholar 

  11. Anversa P, Kajstura J. Ventricular myocytes are not terminally differentiated in the adult mammalian heart. Circ Res. 1998;83:1–14.

    Article  CAS  PubMed  Google Scholar 

  12. Menasche P, Hagege AA, Scorsin M, Pouzet B, Desnos M, Duboc D, Schwartz K, Vilquin JT, Marolleau JP. Myoblast transplantation for heart failure. Lancet. 2001;357:279–80.

    Article  CAS  PubMed  Google Scholar 

  13. Strauer BE, Brehm M, Zeus T, Kostering M, Hernandez A, Sorg RV, Kogler G, Wernet P. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation. 2002;106:1913–8.

    Article  PubMed  Google Scholar 

  14. Erbs S, Linke A, Adams V, Lenk K, Thiele H, Diederich KW, Emmrich F, Kluge R, Kendziorra K, Sabri O, Schuler G, Hambrecht R. Transplantation of blood-derived progenitor cells after recanalization of chronic coronary artery occlusion: first randomized and placebo-controlled study. Circ Res. 2005;97:756–62.

    Article  CAS  PubMed  Google Scholar 

  15. Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Suselbeck T, Assmus B, Tonn T, Dimmeler S, Zeiher AM. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med. 2006;355:1210–21.

    Article  CAS  PubMed  Google Scholar 

  16. Abdel-Latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA, Zuba-Surma EK, Al-Mallah M, Dawn B. Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med. 2007;167:989–97.

    Article  PubMed  Google Scholar 

  17. Menasché P, Hagège AA, Vilquin J-T, Desnos M, Abergel E, Pouzet B, Bel A, Sarateanu S, Scorsin M, Schwartz K, Bruneval P, Benbunan M, Marolleau J-P, Duboc D. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol. 2003;41:1078–83.

    Article  PubMed  Google Scholar 

  18. Siminiak T, Kalawski R, Fiszer D, Jerzykowska O, Rzeźniczak J, Rozwadowska N, Kurpisz M. Autologous skeletal myoblast transplantation for the treatment of postinfarction myocardial injury: phase I clinical study with 12 months of follow-up. Am Heart J. 2004;148:531–7.

    Article  PubMed  Google Scholar 

  19. Afzal MR, Samanta A, Shah ZI, Jeevanantham V, Abdel-Latif A, Zuba-Surma EK, Dawn B. Adult bone marrow cell therapy for ischemic heart disease: evidence and insights from randomized controlled trials. Circ Res. 2015;117:558–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hamano K, Nishida M, Hirata K, Mikamo A, Li TS, Harada M, Miura T, Matsuzaki M, Esato K. Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease: clinical trial and preliminary results. Jpn Circ J. 2001;65:845–7.

    Article  CAS  PubMed  Google Scholar 

  21. Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C, Fichtner S, Korte T, Hornig B, Messinger D, Arseniev L, Hertenstein B, Ganser A, Drexler H. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the boost randomised controlled clinical trial. Lancet. 2004;364:141–8.

    Article  PubMed  Google Scholar 

  22. Meyer GP, Wollert KC, Lotz J, Steffens J, Lippolt P, Fichtner S, Hecker H, Schaefer A, Arseniev L, Hertenstein B, Ganser A, Drexler H. 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;113:1287–94.

    Article  PubMed  Google Scholar 

  23. Schaefer A, Meyer GP, Fuchs M, Klein G, Kaplan M, Wollert KC, Drexler H. Impact of intracoronary bone marrow cell transfer on diastolic function in patients after acute myocardial infarction: results from the boost trial. Eur Heart J. 2006;27:929–35.

    Article  PubMed  Google Scholar 

  24. Meyer GP, Wollert KC, Lotz J, Pirr J, Rager U, Lippolt P, Hahn A, Fichtner S, Schaefer A, Arseniev L, Ganser A, Drexler H. Intracoronary bone marrow cell transfer after myocardial infarction: 5-year follow-up from the randomized-controlled boost trial. Eur Heart J. 2009;30:2978–84.

    Article  PubMed  Google Scholar 

  25. Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T, Endresen K, Ilebekk A, Mangschau A, Fjeld JG, Smith HJ, Taraldsrud E, Grogaard HK, Bjornerheim R, Brekke M, Muller C, Hopp E, Ragnarsson A, Brinchmann JE, Forfang K. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med. 2006;355:1199–209.

    Article  CAS  PubMed  Google Scholar 

  26. Beitnes JO, Hopp E, Lunde K, Solheim S, Arnesen H, Brinchmann JE, Forfang K, Aakhus S. Long-term results after intracoronary injection of autologous mononuclear bone marrow cells in acute myocardial infarction: the astami randomised, controlled study. Heart. 2009;95:1983–9.

    Article  CAS  PubMed  Google Scholar 

  27. 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;28:766–72.

    Article  PubMed  Google Scholar 

  28. Dawn B, Bolli R. Bone marrow for cardiac repair: the importance of characterizing the phenotype and function of injected cells. Eur Heart J. 2007;28:651–2.

    Article  PubMed  Google Scholar 

  29. 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;126:551–68.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Perin EC, Willerson JT, Pepine CJ, Henry TD, Ellis SG, Zhao DX, Silva GV, Lai D, Thomas JD, Kronenberg MW, Martin AD, Anderson RD, Traverse JH, Penn MS, Anwaruddin S, Hatzopoulos AK, Gee AP, Taylor DA, Cogle CR, Smith D, Westbrook L, Chen J, Handberg E, Olson RE, Geither C, Bowman S, Francescon J, Baraniuk S, Piller LB, Simpson LM, Loghin C, Aguilar D, Richman S, Zierold C, Bettencourt J, Sayre SL, Vojvodic RW, Skarlatos SI, Gordon DJ, Ebert RF, Kwak M, Moye LA, Simari RD. Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure: the focus-cctrn trial. JAMA. 2012;307:1717–26.

    Google Scholar 

  31. Traverse JH, Henry TD, Pepine CJ, Willerson JT, Zhao DX, Ellis SG, Forder JR, Anderson RD, Hatzopoulos AK, Penn MS, Perin EC, Chambers J, Baran KW, Raveendran G, Lambert C, Lerman A, Simon DI, Vaughan DE, Lai D, Gee AP, Taylor DA, Cogle CR, Thomas JD, Olson RE, Bowman S, Francescon J, Geither C, Handberg E, Kappenman C, Westbrook L, Piller LB, Simpson LM, Baraniuk S, Loghin C, Aguilar D, Richman S, Zierold C, Spoon DB, Bettencourt J, Sayre SL, Vojvodic RW, Skarlatos SI, Gordon DJ, Ebert RF, Kwak M, Moye LA, Simari RD. 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;308:2380–9.

    Google Scholar 

  32. 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;311:301–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Pompilio G, Nigro P, Bassetti B, Capogrossi MC. Bone marrow cell therapy for ischemic heart disease: the never ending story. Circ Res. 2015;117:490–3.

    Article  CAS  PubMed  Google Scholar 

  34. Gyongyosi M, Wojakowski W, Lemarchand P, Lunde K, Tendera M, Bartunek J, Marban E, Assmus B, Henry TD, Traverse JH, Moye LA, Surder D, Corti R, Huikuri H, Miettinen J, Wohrle J, Obradovic S, Roncalli J, Malliaras K, Pokushalov E, Romanov A, Kastrup J, Bergmann MW, Atsma DE, Diederichsen A, Edes I, Benedek I, Benedek T, Pejkov H, Nyolczas N, Pavo N, Bergler-Klein J, Pavo IJ, Sylven C, Berti S, Navarese EP, Maurer G. Meta-analysis of cell-based cardiac studies (accrue) in patients with acute myocardial infarction based on individual patient data. Circ Res 2015;116:1346–60.

    Google Scholar 

  35. Ang KL, Chin D, Leyva F, Foley P, Kubal C, Chalil S, Srinivasan L, Bernhardt L, Stevens S, Shenje LT, Galinanes M. Randomized, controlled trial of intramuscular or intracoronary injection of autologous bone marrow cells into scarred myocardium during cabg versus cabg alone. Nature clinical practice. Cardiovasc Med. 2008;5:663–70.

    Google Scholar 

  36. Assmus B, Honold J, Schachinger V, Britten MB, Fischer-Rasokat U, Lehmann R, Teupe C, Pistorius K, Martin H, Abolmaali ND, Tonn T, Dimmeler S, Zeiher AM. Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med. 2006;355:1222–32.

    Article  CAS  PubMed  Google Scholar 

  37. Bartunek J, Behfar A, Dolatabadi D, Vanderheyden M, Ostojic M, Dens J, El Nakadi B, Banovic M, Beleslin B, Vrolix M, Legrand V, Vrints C, Vanoverschelde JL, Crespo-Diaz R, Homsy C, Tendera M, Waldman S, Wijns W, Terzic A. Cardiopoietic stem cell therapy in heart failure: the c-cure (cardiopoietic stem cell therapy in heart failure) multicenter randomized trial with lineage-specified biologics. J Am Coll Cardiol. 2013;61:2329–38.

    Article  PubMed  Google Scholar 

  38. Cao F, Sun D, Li C, Narsinh K, Zhao L, Li X, Feng X, Zhang J, Duan Y, Wang J, Liu D, Wang H. Long-term myocardial functional improvement after autologous bone marrow mononuclear cells transplantation in patients with st-segment elevation myocardial infarction: 4 years follow-up. Eur Heart J. 2009;30:1986–94.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Chen SL, Fang WW, Ye F, Liu YH, Qian J, Shan SJ, Zhang JJ, Chunhua RZ, Liao LM, Lin S, Sun JP. Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am J Cardiol. 2004;94:92–5.

    Article  PubMed  Google Scholar 

  40. Colombo A, Castellani M, Piccaluga E, Pusineri E, Palatresi S, Longari V, Canzi C, Sacchi E, Rossi E, Rech R, Gerundini P, Viecca M, Deliliers GL, Rebulla P, Soligo D, Giordano R. 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;12:239–48.

    Google Scholar 

  41. Gao LR, Pei XT, Ding QA, Chen Y, Zhang NK, Chen HY, Wang ZG, Wang YF, Zhu ZM, Li TC, Liu HL, Tong ZC, Yang Y, Nan X, Guo F, Shen JL, Shen YH, Zhang JJ, Fei YX, Xu HT, Wang LH, Tian HT, Liu da Q, Yang Y. A critical challenge: dosage-related efficacy and acute complication intracoronary injection of autologous bone marrow mesenchymal stem cells in acute myocardial infarction. Int J Cardiol. 2013;168:3191–9.

    Article  PubMed  Google Scholar 

  42. Ge J, Li Y, Qian J, Shi J, Wang Q, Niu Y, Fan B, Liu X, Zhang S, Sun A, Zou Y. Efficacy of emergent transcatheter transplantation of stem cells for treatment of acute myocardial infarction (tct-stami). Heart. 2006;92:1764–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Grajek S, Popiel M, Gil L, Breborowicz P, Lesiak M, Czepczynski R, Sawinski K, Straburzynska-Migaj E, Araszkiewicz A, Czyz A, Kozlowska-Skrzypczak M, Komarnicki M. 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.

    Article  PubMed  Google Scholar 

  44. Hendrikx M, Hensen K, Clijsters C, Jongen H, Koninckx R, Bijnens E, Ingels M, Jacobs A, Geukens R, Dendale P, Vijgen J, Dilling D, Steels P, Mees U, Rummens JL. Recovery of regional but not global contractile function by the direct intramyocardial autologous bone marrow transplantation: results from a randomized controlled clinical trial. Circulation. 2006;114:I101–7.

    Article  PubMed  Google Scholar 

  45. Hirsch A, Nijveldt R, van der Vleuten PA, Tijssen JG, van der Giessen WJ, Tio RA, Waltenberger J, ten Berg JM, Doevendans PA, Aengevaeren WR, Zwaginga JJ, Biemond BJ, van Rossum AC, Piek JJ, Zijlstra F. 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;32:1736–47.

    Google Scholar 

  46. Huang RC, Yao K, Zou YZ, Ge L, Qian JY, Yang J, Yang S, Niu YH, Li YL, Zhang YQ, Zhang F, Xu SK, Zhang SH, Sun AJ, Ge JB. Long term follow-up on emergent intracoronary autologous bone marrow mononuclear cell transplantation for acute inferior-wall myocardial infarction. Zhonghua Yi Xue Za Zhi. 2006;86:1107–10.

    PubMed  Google Scholar 

  47. Huikuri HV, Kervinen K, Niemela M, Ylitalo K, Saily M, Koistinen P, Savolainen ER, Ukkonen H, Pietila M, Airaksinen JK, Knuuti J, Makikallio TH. 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;29:2723–32.

    Article  PubMed  Google Scholar 

  48. Janssens S, Dubois C, Bogaert J, Theunissen K, Deroose C, Desmet W, Kalantzi M, Herbots L, Sinnaeve P, Dens J, Maertens J, Rademakers F, Dymarkowski S, Gheysens O, Van Cleemput J, Bormans G, Nuyts J, Belmans A, Mortelmans L, Boogaerts M, Van de Werf F. 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.

    Google Scholar 

  49. Jazi SM, Esfahani MH, Fesharaki M, Moulavi F, Gharipour M. Initial clinical outcomes of intracoronary infusion of autologous progenitor cells in patients with acute myocardial infarction. Arya Atherosc. 2012;7:162–7.

    Google Scholar 

  50. Lipiec P, Krzeminska-Pakula M, Plewka M, Kusmierek J, Plachcinska A, Szuminski R, Robak T, Korycka A, Kasprzak JD. 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;36:587–93.

    Article  PubMed  Google Scholar 

  51. Lu M, Liu S, Zheng Z, Yin G, Song L, Chen H, Chen X, Chen Q, Jiang S, Tian L, He Z, Hu S, Zhao S. A pilot trial of autologous bone marrow mononuclear cell transplantation through grafting artery: a sub-study focused on segmental left ventricular function recovery and scar reduction. Int J Cardiol. 2013;168:2221–7.

    Article  PubMed  Google Scholar 

  52. Lunde K, Solheim S, Forfang K, Arnesen H, Brinch L, Bjornerheim R, Ragnarsson A, Egeland T, Endresen K, Ilebekk A, Mangschau A, Aakhus S. Anterior myocardial infarction with acute percutaneous coronary intervention and intracoronary injection of autologous mononuclear bone marrow cells: safety, clinical outcome, and serial changes in left ventricular function during 12-months' follow-up. J Am Coll Cardiol. 2008;51:674–6.

    Article  PubMed  Google Scholar 

  53. Maureira P, Tran N, Djaballah W, Angioi M, Bensoussan D, Didot N, Fay R, Sadoul N, Villemot JP, Marie PY. Residual viability is a predictor of the perfusion enhancement obtained with the cell therapy of chronic myocardial infarction: a pilot multimodal imaging study. Clin Nucl Med. 2012;37:738–42.

    Article  PubMed  Google Scholar 

  54. Meluzin J, Mayer J, Groch L, Janousek S, Hornacek I, Hlinomaz O, Kala P, Panovsky R, Prasek J, Kaminek M, Stanicek J, Klabusay M, Koristek Z, Navratil M, Dusek L, Vinklarkova J. Autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction: the effect of the dose of transplanted cells on myocardial function. Am Heart J. 2006;152:975.e9–15.

    Google Scholar 

  55. Meluzin J, Janousek S, Mayer J, Groch L, Hornacek I, Hlinomaz O, Kala P, Panovsky R, Prasek J, Kaminek M, Stanicek J, Klabusay M, Koristek Z, Navratil M, Dusek L, Vinklarkova J. Three-, 6-, and 12-month results of autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction. Int J Cardiol. 2008;128:185–92.

    Article  PubMed  Google Scholar 

  56. Nogueira FB, Silva SA, Haddad AF, Peixoto CM, Carvalho RM, Tuche FA, Soares VE, Sousa AL, Rabischoffsky A, Mesquita CT, Borojevic R, Dohmann HF. Systolic function of patients with myocardial infarction undergoing autologous bone marrow transplantation. Arq Bras Cardiol. 2009;93:374–9 .367–372

    Article  PubMed  Google Scholar 

  57. Penicka M, Horak J, Kobylka P, Pytlik R, Kozak T, Belohlavek O, Lang O, Skalicka H, Simek S, Palecek T, Linhart A, Aschermann M, Widimsky P. Intracoronary injection of autologous bone marrow-derived mononuclear cells in patients with large anterior acute myocardial infarction: a prematurely terminated randomized study. J Am Coll Cardiol. 2007;49:2373–4.

    Article  PubMed  Google Scholar 

  58. Perin EC, Silva GV, Henry TD, Cabreira-Hansen MG, Moore WH, Coulter SA, Herlihy JP, Fernandes MR, Cheong BY, Flamm SD, Traverse JH, Zheng Y, Smith D, Shaw S, Westbrook L, Olson R, Patel D, Gahremanpour A, Canales J, Vaughn WK, Willerson JT. A randomized study of transendocardial injection of autologous bone marrow mononuclear cells and cell function analysis in ischemic heart failure (focus-hf). Am Heart J. 2011;161:1078–1087.e1073.

    Google Scholar 

  59. Perin EC, Silva GV, Zheng Y, Gahremanpour A, Canales J, Patel D, Fernandes MR, Keller LH, Quan X, Coulter SA, Moore WH, Herlihy JP, Willerson JT. Randomized, double-blind pilot study of transendocardial injection of autologous aldehyde dehydrogenase-bright stem cells in patients with ischemic heart failure. Am Heart J. 2012;163:415–21.e411.

    Google Scholar 

  60. Piepoli MF, Vallisa D, Arbasi M, Cavanna L, Cerri L, Mori M, Passerini F, Tommasi L, Rossi A, Capucci A. Bone marrow cell transplantation improves cardiac, autonomic, and functional indexes in acute anterior myocardial infarction patients (cardiac study). Eur J Heart Fail. 2010;12:172–80.

    Article  PubMed  Google Scholar 

  61. Piepoli MF, Vallisa D, Arbasi C, Cavanna L, Cerri L, Mori M, Passerini F, Tommasi L, Rossi A, Capucci A. Two year follow-up results of the cardiac (cardiomyoplasty by autologous intracoronary bone marrow in acute myocardial infarction) randomised controlled trial. Int J Cardiol. 2013;168:e132.

    Article  PubMed  Google Scholar 

  62. Plewka M, Krzeminska-Pakula M, Lipiec P, Peruga JZ, Jezewski T, Kidawa M, Wierzbowska-Drabik K, Korycka A, Robak T, Kasprzak JD. Effect of intracoronary injection of mononuclear bone marrow stem cells on left ventricular function in patients with acute myocardial infarction. Am J Cardiol. 2009;104:1336–42.

    Article  PubMed  Google Scholar 

  63. Plewka M, Krzeminska-Pakula M, Peruga JZ, Lipiec P, Kurpesa M, Wierzbowska-Drabik K, Korycka-Wolowiec A, Kasprzak JD. The effects of intracoronary delivery of mononuclear bone marrow cells in patients with myocardial infarction: a two year follow-up results. Kardiol Pol. 2011;69:1234–40.

    PubMed  Google Scholar 

  64. Pokushalov E, Romanov A, Chernyavsky A, Larionov P, Terekhov I, Artyomenko S, Poveshenko O, Kliver E, Shirokova N, Karaskov A, Dib N. Efficiency of intramyocardial injections of autologous bone marrow mononuclear cells in patients with ischemic heart failure: a randomized study. J Cardiovasc Transl Res. 2010;3:160–8.

    Article  PubMed  Google Scholar 

  65. Quyyumi AA, Waller EK, Murrow J, Esteves F, Galt J, Oshinski J, Lerakis S, Sher S, Vaughan D, Perin E, Willerson J, Kereiakes D, Gersh BJ, Gregory D, Werner A, Moss T, Chan WS, Preti R, Pecora AL. Cd34(+) cell infusion after st elevation myocardial infarction is associated with improved perfusion and is dose dependent. Am Heart J. 2011;161:98–105.

    Article  PubMed  Google Scholar 

  66. van Ramshorst J, Bax JJ, Beeres SL, Dibbets-Schneider P, Roes SD, Stokkel MP, de Roos A, Fibbe WE, Zwaginga JJ, Boersma E, Schalij MJ, Atsma DE. Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial. JAMA. 2009;301:1997–2004.

    Article  PubMed  Google Scholar 

  67. Roncalli J, Mouquet F, Piot C, Trochu JN, Le Corvoisier P, Neuder Y, Le Tourneau T, Agostini D, Gaxotte V, Sportouch C, Galinier M, Crochet D, Teiger E, Richard MJ, Polge AS, Beregi JP, Manrique A, Carrie D, Susen S, Klein B, Parini A, Lamirault G, Croisille P, Rouard H, Bourin P, Nguyen JM, Delasalle B, Vanzetto G, Van Belle E, Lemarchand P. Intracoronary autologous mononucleated bone marrow cell infusion for acute myocardial infarction: results of the randomized multicenter bonami trial. Eur Heart J. 2011;32:1748–57.

    Google Scholar 

  68. Ruan W, Pan CZ, Huang GQ, Li YL, Ge JB, Shu XH. Assessment of left ventricular segmental function after autologous bone marrow stem cells transplantation in patients with acute myocardial infarction by tissue tracking and strain imaging. Chin Med J (Engl). 2005;118:1175–81.

    Google Scholar 

  69. Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Suselbeck T, Werner N, Haase J, Neuzner J, Germing A, Mark B, Assmus B, Tonn T, Dimmeler S, Zeiher AM. 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;27:2775–83.

    Article  PubMed  Google Scholar 

  70. Assmus B, Rolf A, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Tillmanns H, Yu J, Corti R, Mathey DG, Hamm CW, Suselbeck T, Tonn T, Dimmeler S, Dill T, Zeiher AM, Schachinger V. Clinical outcome 2 years after intracoronary administration of bone marrow-derived progenitor cells in acute myocardial infarction. Circ Heart Fail. 2010;3:89–96.

    Article  PubMed  Google Scholar 

  71. Silva SA, Sousa AL, Haddad AF, Azevedo JC, Soares VE, Peixoto CM, Soares AJ, Issa AF, Felipe LR, Branco RV, Addad JA, Moreira RC, Tuche FA, Mesquita CT, Drumond CC, Junior AO, Rochitte CE, Luz JH, Rabischoffisky A, Nogueira FB, Vieira RB, Junior HS, Borojevic R, Dohmann HF. Autologous bone-marrow mononuclear cell transplantation after acute myocardial infarction: comparison of two delivery techniques. Cell Transplant. 2009;18:343–52.

    Article  PubMed  Google Scholar 

  72. Srimahachota S, Boonyaratavej S, Rerkpattanapipat P, Wangsupachart S, Tumkosit M, Bunworasate U, Nakorn TN, Intragumtornchai T, Kupatawintu P, Pongam S, Saengsiri AO, Pothisri M, Sukseri Y, Bunprasert T, Suithichaiyakul T. Intra-coronary bone marrow mononuclear cell transplantation in patients with st-elevation myocardial infarction: a randomized controlled study. J Med Assoc Thailand. 2011;94:657–63.

    Google Scholar 

  73. Suarez de Lezo J, Herrera C, Pan M, Romero M, Pavlovic D, Segura J, Sanchez J, Ojeda S, Torres A. [Regenerative therapy in patients with a revascularized acute anterior myocardial infarction and depressed ventricular function]. Rev Espan Cardiol. 2007;60:357–65.

    Google Scholar 

  74. Surder D, Manka R, Lo Cicero V, Moccetti T, Rufibach K, Soncin S, Turchetto L, Radrizzani M, Astori G, Schwitter J, Erne P, Zuber M, Auf-der-Maur C, Jamshidi P, Gaemperli O, Windecker S, Moschovitis A, Wahl A, Buhler I, Wyss C, Kozerke S, Landmesser U, Luscher TF, Corti R. Intracoronary injection of bone marrow-derived mononuclear cells early or late after acute myocardial infarction: effects on global left ventricular function. Circulation. 2013;127:1968–79.

    Article  PubMed  Google Scholar 

  75. Traverse JH, Henry TD, Ellis SG, Pepine CJ, Willerson JT, Zhao DX, Forder JR, Byrne BJ, Hatzopoulos AK, Penn MS, Perin EC, Baran KW, Chambers J, Lambert C, Raveendran G, Simon DI, Vaughan DE, Simpson LM, Gee AP, Taylor DA, Cogle CR, Thomas JD, Silva GV, Jorgenson BC, Olson RE, Bowman S, Francescon J, Geither C, Handberg E, Smith DX, Baraniuk S, Piller LB, Loghin C, Aguilar D, Richman S, Zierold C, Bettencourt J, Sayre SL, Vojvodic RW, Skarlatos SI, Gordon DJ, Ebert RF, Kwak M, Moye LA, Simari RD. Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: the latetime randomized trial. JAMA. 2011;306:2110–9.

    Google Scholar 

  76. Traverse JH, McKenna DH, Harvey K, Jorgenso BC, Olson RE, Bostrom N, Kadidlo D, Lesser JR, Jagadeesan V, Garberich R, Henry TD. 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;160:428–34.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Tse HF, Thambar S, Kwong YL, Rowlings P, Bellamy G, McCrohon J, Thomas P, Bastian B, Chan JK, Lo G, Ho CL, Chan WS, Kwong RY, Parker A, Hauser TH, Chan J, Fong DY, Lau CP. Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (protect-cad trial). Eur Heart J. 2007;28:2998–3005.

    Article  PubMed  Google Scholar 

  78. Turan RG, Bozdag TI, Ortak J, Kische S, Akin I, Schneider H, Turan CH, Rehders TC, Rauchhaus M, Kleinfeldt T, Belu C, Brehm M, Yokus S, Steiner S, Sahin K, Nienaber CA, Ince H. Improved functional activity of bone marrow derived circulating progenitor cells after intra coronary freshly isolated bone marrow cells transplantation in patients with ischemic heart disease. Stem Cell Rev. 2011;7:646–56.

    Article  PubMed  Google Scholar 

  79. Turan RG, Bozdag TI, Turan CH, Ortak J, Akin I, Kische S, Schneider H, Rauchhaus M, Rehders TC, Kleinfeldt T, Belu C, Amen S, Hermann T, Yokus S, Brehm M, Steiner S, Chatterjee T, Sahin K, Nienaber CA, Ince H. Enhanced mobilization of the bone marrow-derived circulating progenitor cells by intracoronary freshly isolated bone marrow cells transplantation in patients with acute myocardial infarction. J Cell Mol Med. 2012;16:852–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Wohrle J, Merkle N, Mailander V, Nusser T, Schauwecker P, von Scheidt F, Schwarz K, Bommer M, Wiesneth M, Schrezenmeier H, Hombach V. Results of intracoronary stem cell therapy after acute myocardial infarction. Am J Cardiol. 2010;105:804–12.

    Article  PubMed  Google Scholar 

  81. Wohrle J, von Scheidt F, Schauwecker P, Wiesneth M, Markovic S, Schrezenmeier H, Hombach V, Rottbauer W, Bernhardt P. Impact of cell number and microvascular obstruction in patients with bone-marrow derived cell therapy: final results from the randomized, double-blind, placebo controlled intracoronary stem cell therapy in patients with acute myocardial infarction (scami) trial. Clin Res Cardiol. 2013;102:765–70.

    Article  PubMed  Google Scholar 

  82. Yao K, Huang R, Qian J, Cui J, Ge L, Li Y, Zhang F, Shi H, Huang D, Zhang S, Sun A, Zou Y, Ge J. Administration of intracoronary bone marrow mononuclear cells on chronic myocardial infarction improves diastolic function. Heart. 2008;94:1147–53.

    Article  CAS  PubMed  Google Scholar 

  83. Yao K, Huang R, Sun A, Qian J, Liu X, Ge L, Zhang Y, Zhang S, Niu Y, Wang Q, Zou Y, Ge J. Repeated autologous bone marrow mononuclear cell therapy in patients with large myocardial infarction. Eur J Heart Fail. 2009;11:691–8.

    Article  PubMed  Google Scholar 

  84. Zhao Q, Sun Y, Xia L, Chen A, Wang Z. Randomized study of mononuclear bone marrow cell transplantation in patients with coronary surgery. Ann Thorac Surg. 2008;86:1833–40.

    Article  PubMed  Google Scholar 

  85. Delewi R, Hirsch A, Tijssen JG, Schachinger V, Wojakowski W, Roncalli J, Aakhus S, Erbs S, Assmus B, Tendera M, Goekmen Turan R, Corti R, Henry T, Lemarchand P, Lunde K, Cao F, Huikuri HV, Surder D, Simari RD, Janssens S, Wollert KC, Plewka M, Grajek S, Traverse JH, Zijlstra F, Piek JJ. Impact of intracoronary bone marrow cell therapy on left ventricular function in the setting of st-segment elevation myocardial infarction: a collaborative meta-analysis. Eur Heart J. 2014;35:989–98.

    Article  PubMed  Google Scholar 

  86. Kandala J, Upadhyay GA, Pokushalov E, Wu S, Drachman DE, Singh JP. Meta-analysis of stem cell therapy in chronic ischemic cardiomyopathy. Am J Cardiol. 2013;112:217–25.

    Article  PubMed  Google Scholar 

  87. Bellenger NG, Burgess MI, Ray SG, Lahiri A, Coats AJ, Cleland JG, Pennell DJ. Comparison of left ventricular ejection fraction and volumes in heart failure by echocardiography, radionuclide ventriculography and cardiovascular magnetic resonance; are they interchangeable? Eur Heart J. 2000;21:1387–96.

    Article  CAS  PubMed  Google Scholar 

  88. Klein C, Nekolla SG, Bengel FM, Momose M, Sammer A, Haas F, Schnackenburg B, Delius W, Mudra H, Wolfram D, Schwaiger M. Assessment of myocardial viability with contrast-enhanced magnetic resonance imaging: comparison with positron emission tomography. Circulation. 2002;105:162–7.

    Article  PubMed  Google Scholar 

  89. Asferg C, Usinger L, Kristensen TS, Abdulla J. Accuracy of multi-slice computed tomography for measurement of left ventricular ejection fraction compared with cardiac magnetic resonance imaging and two-dimensional transthoracic echocardiography: a systematic review and meta-analysis. Eur J Radiol. 2012;81:e757–62.

    Article  PubMed  Google Scholar 

  90. Mansour S, Vanderheyden M, De Bruyne B, Vandekerckhove B, Delrue L, Van Haute I, Heyndrickx G, Carlier S, Rodriguez-Granillo G, Wijns W, Bartunek J. 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;47:1727–30.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Buddhadeb Dawn M.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Samanta, A., Afzal, M.R., Dawn, B. (2017). Bone Marrow Cell Therapy for Ischemic Heart Disease and the Role of Cardiac Imaging in Evaluation of Outcomes. In: Pandey, T. (eds) Imaging in Stem Cell Transplant and Cell-based Therapy. Stem Cell Biology and Regenerative Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-51833-6_9

Download citation

Publish with us

Policies and ethics