Skip to main content
Journal of Cellular and Molecular Medicine logoLink to Journal of Cellular and Molecular Medicine
. 2007 May 1;10(3):727–733. doi: 10.1111/j.1582-4934.2006.tb00432.x

Intracoronary infusion of autologous bone marrow cells and left ventricular function after acute myocardial infarction: a meta-analysis

M Hristov a, Nicole Heussen b, A Schober c, C Weber a,*
PMCID: PMC3933154  PMID: 16989732

Abstract

Recent clinical studies have demonstrated that intracoronary infusion of autologous bone marrow cells (BMC) in conjunction with standard treatment may improve left ventricular function after an acute myocardial infarction (AMI). However, the results of these studies remain controversial, as the studies were relatively small in size and partially differed in design. We reviewed primary controlled randomized clinical studies comparing intracoronary transfer of autologous non-mobilized BMC combined with standard therapy versus standard therapy alone in patients with AMI. We identified five randomized controlled clinical trials, three of which were also placebo- and bone marrow aspiration-controlled. Non-mobilized BMC were infused into the revascularized coronary target artery 6.6 ± 6.1 days after AMI. The mean follow-up period of 5.2 ± 1.1 months was completed by 482 patients, 241 of which received infusion of BMC. The effect of BMC on left ventricular ejection fraction (LVEF) as a major functional parameter was evaluated. Analyzing the overall effect on the change in LVEF between baseline and follow-up value revealed a significant improvement in the BMCtreated group as compared to the control group (P = 0.04). Thus, considering the increase in LVEF during follow-up, transplantation of BMC may be a safe and beneficial procedure to support treatment of AMI. However, the functional improvement observed with this form of therapy was altogether relatively moderate and the studies were heterogeneous in design. Hence, further efforts aiming at large-scale, double-blind, randomized and placebo-controlled multi-center trials in conjunction with better definition of patients, which benefit from BMC infusion, appear to be warranted.

Keywords: myocardial infarction, revascularization, bone marrow, follow-up studies, meta-analysis

References

  • 1.Dimmeler S, Zeiher AM, Schneider MD. Unchain my heart: the scientific foundations of cardiac repair. J Clin Invest. 2005;115:572–83. doi: 10.1172/JCI24283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Hristov M, Weber C. The therapeutic potential of progenitor cells in ischemic heart disease: past, present and future. Basic Res Cardiol. 2006;101:1–7. doi: 10.1007/s00395-005-0573-0. [DOI] [PubMed] [Google Scholar]
  • 3.Mathur A, Martin JF. Stem cells and repair of the heart. Lancet. 2004;364:183–92. doi: 10.1016/S0140-6736(04)16632-4. [DOI] [PubMed] [Google Scholar]
  • 4.Perin EC, Geng YJ, Willerson JT. Adult stem cell therapy in perspective. Circulation. 2003;107:935–8. doi: 10.1161/01.cir.0000057526.10455.bd. [DOI] [PubMed] [Google Scholar]
  • 5.Zernecke A, Schober A, Bot I, von Hundelshausen P, Liehn EA, Mopps B, Mericskay M, Gierschik P, Biessen EA, Weber C. SDF-1alpha/CXCR4 axis is instrumental in neointimal hyperplasia and recruitment of smooth muscle progenitor cells. Circ Res. 2005;96:784–91. doi: 10.1161/01.RES.0000162100.52009.38. [DOI] [PubMed] [Google Scholar]
  • 6.Yoon YS, Wecker A, Heyd L, Park JS, Tkebuchava T, Kusano K, Hanley A, Scadova H, Qin G, Cha DH, Johnson KL, Aikawa R, Asahara T, Losordo DW. Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. J Clin Invest. 2005;115:326–38. doi: 10.1172/JCI22326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.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. doi: 10.1038/86498. [DOI] [PubMed] [Google Scholar]
  • 8.Nygren JM, Jovinge S, Breitbach M, Sawen P, Roll W, Hescheler J, Taneera J, Fleischmann BK, Jacobsen SE. Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nat Med. 2004;10:494–501. doi: 10.1038/nm1040. [DOI] [PubMed] [Google Scholar]
  • 9.Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, Pasumarthi KB, Virag JI, Bartelmez SH, Poppa V, Bradford G, Dowell JD, Williams DA, Field LJ. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature. 2004;428:664–8. doi: 10.1038/nature02446. [DOI] [PubMed] [Google Scholar]
  • 10.Ziegelhoeffer T, Fernandez B, Kostin S, Heil M, Voswinckel R, Helisch A, Schaper W. Bone marrowderived cells do not incorporate into the adult growing vasculature. Circ Res. 2004;94:230–8. doi: 10.1161/01.RES.0000110419.50982.1C. [DOI] [PubMed] [Google Scholar]
  • 11.Heil M, Ziegelhoeffer T, Mees B, Schaper W. A different outlook on the role of bone marrow stem cells in vascular growth: bone marrow delivers software not hardware. Circ Res. 2004;94:573–4. doi: 10.1161/01.RES.0000124603.46777.EB. [DOI] [PubMed] [Google Scholar]
  • 12.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. doi: 10.1161/01.cir.0000034046.87607.1c. [DOI] [PubMed] [Google Scholar]
  • 13.Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N, Grunwald F, Aicher A, Urbich C, Martin H, Hoelzer D, Dimmeler S, Zeiher AM. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI) Circulation. 2002;106:3009–17. doi: 10.1161/01.cir.0000043246.74879.cd. [DOI] [PubMed] [Google Scholar]
  • 14.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. doi: 10.1016/j.amjcard.2004.03.034. [DOI] [PubMed] [Google Scholar]
  • 15.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. doi: 10.1016/S0140-6736(04)16626-9. [DOI] [PubMed] [Google Scholar]
  • 16.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;367:113–21. doi: 10.1016/S0140-6736(05)67861-0. [DOI] [PubMed] [Google Scholar]
  • 17.Lunde K. 2005. Nov 16, Effects on left ventricular function by intracoronary injections of autologous mononuclear bone marrow cells in acute anterior wall myocardial infarction: the ASTAMI randomized controlled trial. Late-breaking clinical trial reported at the plenary scientific sessions of the American Heart Association Meeting, Dallas,
  • 18.Schachinger V. 2005. Nov 13, Intracoronary infusion of bone marrowderived progenitor cells in acute myocardial infarction: a randomized, double-blind, placebo-controlled multicenter trial (REPAIR-AMI). Late-breaking clinical trial reported at the plenary scientific sessions of the American Heart Association Meeting, Dallas,
  • 19.DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88. doi: 10.1016/0197-2456(86)90046-2. [DOI] [PubMed] [Google Scholar]
  • 20.Kang HJ, Kim HS, Zhang SY, Park KW, Cho HJ, Koo BK, Kim YJ, Soo Lee D, Sohn DW, Han KS, Oh BH, Lee MM, Park YB. 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;363:751–6. doi: 10.1016/S0140-6736(04)15689-4. [DOI] [PubMed] [Google Scholar]
  • 21.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. doi: 10.1161/01.RES.0000185811.71306.8b. [DOI] [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;113:1272–4. doi: 10.1161/CIRCULATIONAHA.105.575118. [DOI] [PubMed] [Google Scholar]
  • 23.Hristov M, Weber C. Endothelial progenitor cells: characterization, pathophysiology, and possible clinical relevance. J Cell Mol Med. 2004;8:498–508. doi: 10.1111/j.1582-4934.2004.tb00474.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Hristov M, Fach C, Becker C, Heussen N, Liehn EA, Blindt R, Hanrath P, Weber C. 2006. Reduced numbers of circulating endothelial progenitor cells in patients with coronary artery disease associated with long-term statin treatment Atherosclerosis ; in press. [DOI] [PubMed]
  • 25.Penn MS. Stem-cell therapy after acute myocardial infarction: the focus should be on those at risk. Lancet. 2006;367:87–88. doi: 10.1016/S0140-6736(05)67895-6. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Cellular and Molecular Medicine are provided here courtesy of Blackwell Publishing

RESOURCES