99
Views
10
CrossRef citations to date
0
Altmetric
Review

Cell therapy for heart failure: the need for a new therapeutic strategy

&
Pages 1107-1126 | Published online: 10 Jan 2014

References

  • Lloyd-Jones D, Adams RJ, Brown TM et al. Heart Disease and Stroke Statistics – 2010 Update: a report from the American Heart Association. Circulation121(7), e46–e215 (2010).
  • Triposkiadis F, Karayannis G, Giamouzis G, Skoularigis J, Louridas G, Butler J. The sympathetic nervous system in heart failure: physiology, pathophysiology, and clinical implications. J. Am. Coll. Cardiol.54(19), 1747–1762 (2009).
  • Swedberg K, Held P, Kjekshus J, Rasmussen K, Ryden L, Wedel H. Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction. Results of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II). N. Engl. J. Med.327(10), 678–684 (1992).
  • Pfeffer MA, Braunwald E, Moye LA et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N. Engl J. Med.327(10), 669–677 (1992).
  • Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. The SOLVD Investigators. N. Engl J. Med.327(10), 685–691 (1992).
  • Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators. N. Engl J. Med.325(5), 293–302 (1991).
  • Bristow MR, Gilbert EM, Abraham WT et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. Circulation94(11), 2807–2816 (1996).
  • Investigatros M-H. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in-Congestive Heart Failure (MERIT-HF). Lancet353(9169), 2001–2007 (1999).
  • Packer M, Coats AJS, Fowler MB et al. Effect of carvedilol on survival in severe chronic heart failure. N. Engl. J. Med.344(22), 1651–1658 (2001).
  • Packer M, Poole-Wilson PA, Armstrong PW et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. Circulation100(23), 2312–2318 (1999).
  • Pitt B, Remme W, Zannad F et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N. Engl. J. Med.348(14), 1309–1321 (2003).
  • Pitt B, Zannad F, Remme WJ et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N. Engl. J. Med.341(10), 709–717 (1999).
  • Cohn JN, Tognoni G; the Valsartan Heart Failure Trial I. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N. Engl. J. Med.345(23), 1667–1675 (2001).
  • Anand PI, McMurray PJ, Cohn PJN et al. Long-term effects of darusentan on left-ventricular remodelling and clinical outcomes in the EndothelinA Receptor Antagonist Trial in Heart Failure (EARTH): randomised, double-blind, placebo-controlled trial. Lancet364(9431), 347–354 (2004).
  • Rogers JG, Butler J, Lansman SL et al. Chronic mechanical circulatory support for inotrope-dependent heart failure patients who are not transplant candidates: results of the INTREPID trial. J. Am. Coll. Cardiol.50(8), 741–747 (2007).
  • Birks EJ, Tansley PD, Hardy J et al. Left ventricular assist device and drug therapy for the reversal of heart failure. N. Engl. J. Med.355(18), 1873–1884 (2006).
  • Abraham WT, Fisher WG, Smith AL et al. Cardiac resynchronization in chronic heart failure. N. Engl. J. Med.346(24), 1845–1853 (2002).
  • Abraham WT, Young JB, Leon AR et al. Effects of cardiac resynchronization on disease progression in patients with left ventricular systolic dysfunction, an indication for an implantable cardioverter-defibrillator, and mildly symptomatic chronic heart failure. Circulation110(18), 2864–2868 (2004).
  • Bristow MR, Saxon LA, Boehmer J et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N. Engl. J. Med.350(21), 2140–2150 (2004).
  • Cleland JGF, Daubert J-C, Erdmann E et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N. Engl. J. Med.352(15), 1539–1549 (2005).
  • St John Sutton MG, Plappert T, Abraham WT et al. Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure. Circulation107(15), 1985–1990 (2003).
  • Fukuda K, Yuasa S. Stem cells as a source of regenerative cardiomyocytes. Circ. Res.98(8), 1002–1013 (2006).
  • Thomson JA, Itskovitz-Eldor J, Shapiro SS et al. Embryonic stem cell lines derived from human blastocysts. Science282, 1145–1147 (1998).
  • Blocklet D, Toungouz M, Berkenboom G et al. Myocardial homing of nonmobilized peripheral-blood CD34+ cells after intracoronary injection. Stem Cells24(2), 333–336 (2006).
  • Hofmann M, Wollert KC, Meyer GP et al. Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation111(17), 2198–2202 (2005).
  • Kang W, Kang H-J, Kim H, Chung J, Lee M, Lee D. Tissue distribution of 18F-FDG-labeled peripheral hematopoietic stem cells after intracoronary administration in patients with myocardial infarction. J. Nucl. Med.47, 1295–1301 (2006).
  • Penicka M, Widimsky P, Kobylka P, Kozak T, Lang O. Early tissue distribution of bone marrow mononuclear cells after transcoronary transplantation in a patient with acute myocardial infarction. Circulation112(4), e63–65 (2005).
  • Schachinger V, Aicher A, Dobert N et al. Pilot trial on determinants of progenitor cell recruitment to the infarcted human myocardium. Circulation118(14), 1425–1432 (2008).
  • Schots R, De Keulenaer G, Schoors D et al. Evidence that intracoronary-injected CD133+ peripheral blood progenitor cells home to the myocardium in chronic postinfarction heart failure. Exp. Hematol.35(12), 1884–1890 (2007).
  • Brasselet C, Morichetti MC, Messas E et al. Skeletal myoblast transplantation through a catheter-based coronary sinus approach: an effective means of improving function of infarcted myocardium. Eur. Heart J.26(15), 1551–1556 (2005).
  • Hare JM, Traverse JH, Henry TD et al. A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (Prochymal) after acute myocardial infarction. J. Am. Coll. Cardiol.54(24), 2277–2286 (2009).
  • Freyman T, Polin G, Osman H et al. A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. Eur. Heart J.27(9), 1114–1122 (2006).
  • Hou D, Youssef EA-S, Brinton TJ et al. Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials. Circulation112(Suppl. 9), I150–I156 (2005).
  • Perin EC, Silva GV, Assad JAR et al. Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction. J. Mol. Cell. Cardiol.44(3), 486–495 (2008).
  • Bartunek J, Sherman W, Vanderheyden M, Fernandez-Aviles F, Wijns W, Terzic A. Delivery of biologics in cardiovascular regerative medicine. Clin. Pharmacol. Ther.85(5), 548–552 (2009).
  • Sekiya S, Shimizu T, Yamato M, Kikuchi A, Okano T. Bioengineered cardiac cell sheet grafts have intrinsic angiogenic potential. Biochem. Biophys. Res. Commun.341(2), 573–582 (2006).
  • Kobayashi H, Shimizu T, Yamato M et al. Fibroblast sheets co-cultured with endothelial progenitor cells improve cardiac function of infarcted hearts. J. Artif. Organs11(3), 141–147 (2008).
  • Masuda S, Shimizu T, Yamato M, Okano T. Cell sheet engineering for heart tissue repair. Adv. Drug Deliv. Rev.60(2), 277–285 (2008).
  • Badie N, Sattewhite L, Bursac N. A method to replicate the microstructure of heart tissue in vitro using DTMRI-based micropatterning. Ann. Biomed. Eng.37(12), 1512–1521 (2009).
  • Bursac N. Cardiac tissue engineering using stem cells. IEEE Eng. Med. Biol. Mag.28(2), 82–89 (2009).
  • Tongers J, Webber MJ, Losordo DW. Bioengineering to enhance progenitor cell therapeutics. Tex. Heart Inst. J.36(2), 140–144 (2009).
  • Assmus B, Honold J, Schachinger V et al. Transcoronary transplantation of progenitor cells after myocardial infarction. N. Engl. J. Med.355(12), 1222–1232 (2006).
  • Assmus B, Schachinger V, Teupe C et al. Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation106, 3009–3017 (2002).
  • Bartunek J, Vanderheyden M, Vandekerckhove B et al. Intracoronary injection of CD133-positive enriched bone marrow progenitor cells promotes cardiac recovery after recent myocardial infarction: feasibility and safety. Circulation112(Suppl. 9), I178–I183 (2005).
  • Britten M, Abolmaali ND, Assmus B et al. Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI). Circulation108(18), 2212–2218 (2003).
  • Chen S-l, Fang W-w, Ye F et al. Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am. J. Cardiol.94(1), 92–95 (2004).
  • Dobert N, Britten M, Assmus B et al. Transplantation of progenitor cells after reperfused acute myocardial infarction: evaluation of perfusion and myocardial viability with FDG-PET and thallium SPECT. Eur. J. Nuc. Med. Mol. Imaging31(8), 1146–1151 (2004).
  • Ge J, Li Y, Qian J et al. Efficacy of emergent transcatheter transplantation of stem cells for treatment of acute myocardial infarction (TCT-STAMI). Heart92(12), 1764–1767 (2006).
  • Huikuri HV, Kervinen K, Niemela M et al. 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.29(22), 2723–2732 (2008).
  • 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. Lancet367(9505), 113–121 (2006).
  • Kang H-J, Kim H-S, Zhang S-Y et al. Effects of intracoronary infusion of peripheral blood stem-cells mobilized with granulocyte-colony stimulating factor on left ventricular systolic function and restensis after coronary stenting in myocardial infarction: the MAGIC Cell randomised clinical trial. Lancet363, 751–756 (2004).
  • Kang H-J, Lee H-Y, Na S-H et al. Differential effect of intracoronary infusion of mobilized peripheral blood stem cells by granulocyte colony-stimulating factor on left ventricular function and remodeling in patients with acute myocardial infarction versus old myocardial infarction: the MAGIC Cell-3-DES randomized, controlled trial. Circulation114(Suppl. 1), I145–I151 (2006).
  • Kucia M, Dawn B, Hunt G et al. Cells expressing early cardiac markers reside in the bone marrow and are mobilized into the peripheral blood after myocardial infarction. Circ. Res.95(12), 1191–1199 (2004).
  • Li Z, Ming Z, Yuan-zhe J et al. The clinical study of autologous peripheral blood stem cell transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI). Int. J. Cardiol.115(1), 52–56 (2007).
  • Lunde K, Solheim S, Aakhus S et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N. Engl. J. Med.355, 1199–1209 (2006).
  • Lunde K, Solheim S, Forfang Kr et al. 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.51(6), 674–676 (2008).
  • Meluzín J, Mayer J, Groch L et al. 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.152(5), 975.e979–975.e915 (2006).
  • Nijveldt R, Hirsch A, Van der Vleuten P et al. Intracoronary infusion of mononuclear cells after primary percutaneous coronary intervention: the HEBE trial. Circulation118(22), 2316 (2008).
  • Schachinger V, Erbs S, Elsasser A et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N. Engl. J. Med.355(12), 1210–1221 (2006).
  • Schachinger V, Erbs S, Elsasser A et al. 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.27(23), 2775–2783 (2006).
  • Stamm C, Westphal B, Kleine H-D et al. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet361, 45–46 (2003).
  • Strauer BE, Brehm M, Zeus T et al. Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT study. J. Am. Coll. Cardiol.46(9), 1651–1658 (2005).
  • Strauer BE, Brehm M, Zeus T et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation106, 1913–1918 (2002).
  • Tendera M, Wojakowski W, Ruzyllo W et al. Intracoronary infusion of bone marrow-derived selected CD34+CXCR4+ cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) trial. Eur. Heart J.30(11), 1313–1321 (2009).
  • Wollert KC, Meyer GP, Lotz J et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet364, 141–148 (2004).
  • Yousef M, Schannwell CM, Köstering M, Zeus T, Brehm M, Strauer BE. The BALANCE study: clinical benefit and long-term outcome after intracoronary autologous bone marrow cell transplantation in patients with acute myocardial infarction. J. Am. Coll. Cardiol.53(24), 2262–2269 (2009).
  • Hrobjartsson A, Gotzsche PC. Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. N. Engl. J. Med.344(21), 1594–1602 (2001).
  • Kaptchuk TJ, Goldman P, Stone DA, Stason WB. Do medical devices have enhanced placebo effects? J. Clin. Epidemiol.53(8), 786–792 (2000).
  • Ruan W, Pan C, Huang G, Li Y, Ge J, Shu X. Assessment of left ventricular segmental function after autologous bone marrow sten cells transplantation in patients with acute myocardial infarction by tissue tracking and strain imaging. Chin. Med. J. (Engl.)118, 1175–1181 (2005).
  • Hendrikx M, Hensen K, Clijsters C et al. Recovery of regional but not global contractile function by the direct intramyocardial autologous bone marrow transplantation: results from a randomized controlled clinical trial. Circulation114(Suppl. 1), I101–I107 (2006).
  • 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. Circulation113(10), 1287–1294 (2006).
  • Abdel-Latif A, Bolli R, Tleyjeh IM et al. Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch. Intern. Med.167(10), 989–997 (2007).
  • Hristov M, Heussen N, Schober A, Weber C. Intracoronary infusion of autologous bone marrow cells and left ventricular function after acute myocardial infarction: a meta-analysis. J. Cell. Mol. Med.10(3), 727–733 (2006).
  • Lipinski MJ, Biondi-Zoccai GGL, Abbate A et al. Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction: a collaborative systematic review and meta-analysis of controlled clinical trials. J. Am. Coll. Cardiol.50(18), 1761–1767 (2007).
  • Burt RK, Loh Y, Pearce W et al. Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases. JAMA299(8), 925–936 (2008).
  • 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.28(6), 766–772 (2007).
  • Jolicoeur EM, Granger CB, Fakunding JL et al. Bringing cardiovascular cell-based therapy to clinical application: perspectives based on a National Heart, Lung, and Blood Institute Cell Therapy Working Group meeting. Am. Heart J.153(5), 732–742 (2007).
  • Kissel CK, Lehmann R, Assmus B et al. Selective functional exhaustion of hematopoietic progenitor cells in the bone marrow of patients with postinfarction heart failure. J. Am. Coll. Cardiol.49(24), 2341–2349 (2007).
  • Assmus B, Fischer-Rasokat U, Honold J et al. Transcoronary transplantation of functionally competent BMCs is associated with a decrease in natriuretic peptide serum levels and improved survival of patients with chronic postinfarction heart failure: results of the TOPCARE-CHD registry. Circ. Res.100(8), 1234–1241 (2007).
  • Heeschen C, Lehmann R, Honold J et al. Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease. Circulation109, 1615–1622 (2004).
  • Amado LC, Saliaris AP, Schuleri KH et al. Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc. Natl Acad. Sci. USA102(32), 11474–11479 (2005).
  • Gnecchi M, He H, Liang OD et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat. Med.11(4), 367–368 (2005).
  • Gnecchi M, He H, Noiseux N et al. Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J.20(6), 661–669 (2006).
  • Mangi AA, Noiseux N, Kong D et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat. Med.9(9), 1195–1201 (2003).
  • Traverse JH, Henry TD, Vaughn DE et al. Rationale and design for TIME: a Phase II, randomized, double-blind, placebo-controlled pilot trial evaluating the safety and effect of timing of administration of bone marrow mononuclear cells after acute myocardial infarction. Am. Heart J.158(3), 356–363 (2009).
  • Blatt A, Cotter G, Leitman M et al. Intracoronary administration of autologous bone marrow mononuclear cells after induction of short ischemia is safe and may improve hibernation and ischemia in patients with ischemic cardiomyopathy. American Heart Journal150(5), 986.e1–986.e7 (2005).
  • Fuchs S, Satler LF, Kornowski R et al. Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease. J. Am. Coll. Cardiol.41, 1721–1724 (2003).
  • Hamano K, Nishida M, Hirata K et al. Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease. Jpn Circ. J.65, 845–847 (2001).
  • Losordo DW, Schatz RA, White CJ et al. Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: a Phase I/IIa double-blind, randomized controlled trial. Circulation115(25), 3165–3172 (2007).
  • Tse H-F, Kwong Y-L, Chan JKF, Lo G, Ho C-L, Lau C-P. Angiogenesis in ischaemic mocardium by intramyocardial autologous bone marrow mononuclear cell transplantation. Lancet361, 47–49 (2003).
  • Losordo DW, Henry T, Schatz RA et al. Abstract 5638: Autologous CD34+ cell therapy for refractory angina: 12 month results of the Phase II ACT34-CMI Study. Circulation120, S1132 (2009).
  • Stone PH, Gratsiansky NA, Blokhin A, Huang IZ, Meng L. Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J. Am. Coll. Cardiol.48(3), 566–575 (2006).
  • Pompili V. SEACOAST: Results of CD133+ cells for CMI. Presented at: The Third International Conference for Cell Therapy for Cardiovascular Disease. New York, NY, USA, 17–19 January 2007.
  • Galinanes M, Loubani M, Davies J, Chin D, Pasi J, Bell PR. Autotransplantation of unmanipulated bone marrow into scarred myocardium is safe and enhances cardiac function in humans. Cell Transplant.13(1), 7–13 (2004).
  • Gao LR, Wang ZG, Zhu ZM et al. Effect of intracoronary transplantation of autologous bone marrow-derived mononuclear cells on outcomes of patients with refractory chronic heart failure secondary to ischemic cardiomyopathy. Am. J. Cardiol.98(5), 597–602 (2006).
  • Hill JM, Bartunek J. The end of granulocyte colony-stimulating factor in acute myocardial infarction? Reaping the benefits beyond cytokine mobilization Circulation113(16), 1926–1928 (2006).
  • Ozbaran M, Omay SB, Nalbantgil S et al. Autologous peripheral stem cell transplantation in patients with congestive heart failure due to ischemic heart disease. Eur. J. Cardiothorac. Surg.25, 342–351 (2004).
  • Patel AN, Geffner L, Vina RF et al. Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: a prospective randomized study. J. Thorac. Cardiovasc. Surg.130(6), 1631 (2005).
  • Perin EC, Dohmann HFR, Borojevic R et al. Transendocardial, autologous bone marrow cell transplantation for severe chronic ischemic heart failure. Circulation107, 2294–2302 (2003).
  • Perin EC, Silva GV, Zheng Y et al. Abstract 3502: First in man transendocardial injection of autologous aldehyde dehydrogenase-bright cells in heart failure patients (FOCUS-Bright). Circulation120(18 MeetingAbstracts), S812 (2009).
  • Dib N, Henry T, DeMaria A et al. Abstract 3493: The first US study to assess the feasibility and safety of endocardial delivery of allogenic mesenchymal precursor cells in patient with heart failure: three-month interim analysis. Circulation120(18), S810b (2009).
  • Schannwell CM, Yousef M, Basalyk CM et al. Abstract 2390: Dusseldorfer-ABCD trial (Autologous Bone Marrow Cells in Dilated Cardiomyopathy). Circulation118(18), S716 (2008).
  • Seth S, Narang R, Bhargava B et al. Percutaneous intracoronary celullar cardiomyoplasty for nonischemic cardiomyopathy: clinical and histopathological results: the first-in-man ABCE (Autologous Bone Marrow Cells in Dilated Cardiomyopathy) trial. J. Am. Coll. Cardiol.48, 2350–2351 (2006).
  • Bearzi C, Rota M, Hosoda T et al. Human cardiac stem cells. Proc. Natl Acad. Sci. USA104(35), 14068–14073 (2007).
  • Urbanek K, Torella D, Sheikh F et al. Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc. Natl Acad. Sci. USA102(24), 8692–8697 (2005).
  • Manginas A, Goussetis E, Koutelou M et al. Pilot study to evaluate the safety and feasibility of intracoronary CD133+ and CD133+ CD34+ cell therapy in patients with nonviable anterior myocardial infarction. Catheter. Cardiovasc. Interv.69(6), 773–781 (2007).
  • Archundia A, Aceves J, Lopez-Hernandez M et al. Direct cardiac injection of G-CSF mobilized bone-marrow stem-cells improves ventricular function in Old myocardial infarction. Life Sci.79, 279–283 (2005).
  • Menasche P, Hagege AA, Vilquin J-T et al. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J. Am. Coll. Cardiol.41(7), 1078–1083 (2003).
  • Taylor DA, Atkins BZ, Hungsprugs P et al. Regenerating functional myocardium: Improved performance after skeletal myobalst transplantation. Nat. Med.4(8), 929–933 (1998).
  • Scorsin M, Hagège A, Vilquin J-T et al. Comparison of the effects of fetal cardiomyocyte and skeletal myoblast transplantation on postinfarction left ventricular function. J. Thorac. Cardiovasc. Surg.119(6), 1169–1175 (2000).
  • Law P. First human heart myoblast allograft. Circulation110(Suppl. III), 39 (2004).
  • Taylor DA. Cell-based myocardial repair: how should we proceed? Int. J. Cardiol.95(Suppl. 1), S8–S12 (2004).
  • Dib N, Michler RE, Pagani FD et al. Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: four-year follow-up. Circulation112(12), 1748–1755 (2005).
  • Gavira JJ, Herreros Js, Perez A et al. Autologous skeletal myoblast transplantation in patients with nonacute myocardial infarction: 1-year follow-up. J. Thorac. Cardiovasc. Surg.131(4), 799–804 (2006).
  • Hagege AA, Marolleau J-P, Vilquin J-T et al. Skeletal myoblast transplantation in ischemic heart failure: long-term follow-up of the first Phase I cohort of patients. Circulation114(Suppl. 1), I108–I113 (2006).
  • He K-L, Yi G-H, Sherman W et al. Autologous skeletal myoblast transplantation improved hemodynamics and left ventricular function in chronic heart failure dogs. J. Heart Lung Transplant.24(11), 1940–1949 (2005).
  • Herreros J, Prosper F, Perez A et al. Autologous intramyocardial injection of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction. Eur. Heart J.24(22), 2012–2020 (2003).
  • Ince Hs, Petzsch M, Rehders TC, Chatterjee T, Nienaber CA. Transcatheter transplantation of autologous skeletal myoblasts in postinfarction patients with severe left ventricular dysfunction. J. Endovasc. Ther.11(6), 695–704 (2004).
  • Siminiak T, Fiszer D, Jerzykowska O et al. Percutaneous trans-coronary-venous transplantation of autologous skeletal myoblasts in the treatment of post-infarction myocardial contractility impairment: the POZNAN trial. Eur. Heart J.26(12), 1188–1195 (2005).
  • Siminiak T, Kalawski R, Fiszer D et al. Autologous skeletal myoblast transplantation for the treatment of postinfarction myocardial injury: Phase I clinical study with 12 months of follow-up. Am. Heart J.148(3), 531–537 (2004).
  • Smits PC, van Geuns R-JM, Poldermans D et al. Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up. J. Am. Coll. Cardiol.42(12), 2063–2069 (2003).
  • Chachques JC, Duarte F, Cattadori B et al. Angiogenic growth factors and/or cellular therapy for myocardial regeneration: a comparative study. J. Thorac. Cardiovasc. Surg.128(2), 245–253 (2004).
  • Sherman W. MYOHEART US Phase I study: 12 month data. Presented at: The Fifth Annual Conference on Cell Therapy for Cardiovascular Disease. New York, NY, USA, 13–16 January 2009.
  • Dib N, Dinsmore J, Lababidi Z et al. One-year follow-up of feasibility and safety of the first U.S., randomized, controlled study using 3-dimensional guided catheter-based delivery of autologous skeletal myoblasts for ischemic cardiomyopathy (CAUSMIC study). JACC Cardiovasc. Interv.2(1), 9–16 (2009).
  • Abraham MR, Henrikson CA, Tung L et al. Antiarrhythmic engineering of skeletal myoblasts for cardiac transplantation. Circ. Res.97(2), 159–167 (2005).
  • Serruys P. Final results of a Phase II, randomized, open-label trial to evaluate intramyocardial autologous skeletal myoblast transplantation in congestive heart failure patients: the SEISMIC trial. In: American College of Cardiology Scientific Sessions – Late Breaking Clinical Trials. Chicago, IL, USA (2008).
  • Povsic T, Henry T, Taussig A et al. MARVEL-1: a double-blind, randomized, controlled, multicenter study to assess the safety and cardiovascular effects of myocell implantation by a catheter delivery system in congestive heart failure patients post myocardial infarction(s). J. Card. Fail.15(9), 814–815 (2009).
  • Menasche P, Alfieri O, Janssens S et al. The myoblast autologous grafting in ischemic cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation117(9), 1189–1200 (2008).
  • Muller P, Pfeiffer P, Koglin J et al. Cardiomyocytes of noncardiac origin in myocardial biopsies of human transplanted hearts. Circulation106, 31–35 (2002).
  • Quaini F, Urbanek K, Beltrami AP et al. Chimerism of the transplanted heart. N. Eng. J. Med.346(1), 5–15 (2002).
  • Orlic D, Kajstura J, Chimenti S et al. Bone marrow cells regenerate infarcted myocardium. Nature410, 701–705 (2001).
  • Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature428, 668–673 (2004).
  • Murry CE, Soonpaa MH, Reinecke H et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature328, 664–668 (2004).
  • Dimmeler S, Burchfield J, Zeiher AM. Cell-based therapy of myocardial infarction. Arterioscler. Thromb. Vasc. Biol.28(2), 208–216 (2008).
  • Gnecchi M, Zhang Z, Ni A, Dzau VJ. Paracrine mechanisms in adult stem cell signaling and therapy. Circ. Res.103(11), 1204–1219 (2008).
  • Uemura R, Xu M, Ahmad N, Ashraf M. Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. Circ. Res.98(11), 1414–1421 (2006).
  • Wollert KC, Drexler H. Clinical applications of stem cells for the heart. Circ. Res.96(2), 151–163 (2005).
  • Anversa P, Leri A, Kajstura J. Cardiac regeneration. J. Am. Coll. Cardiol.47(9), 1769–1776 (2006).
  • Beltrami AP, Barlucchi L, Torella D et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell114(6), 763–776 (2003).
  • Beltrami AP, Urbanek K, Kajstura J et al. Evidence that human cardiac myocytes divide after myocardial infarction. N. Engl. J. Med.344(23), 1750–1757 (2001).
  • Kajstura J, Rota M, Whang B et al. Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion. Circ. Res.96(1), 127–137 (2005).
  • Messina E, De Angelis L, Frati G et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ. Res.95(9), 911–921 (2004).
  • Smith RR, Barile L, Cho HC et al. Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation115(7), 896–908 (2007).
  • Fransioli J, Bailey B, Gude NA et al. Evolution of the c-kit-positive cell response to pathological challenge in the myocardium. Stem Cells26(5), 1315–1324 (2008).
  • Laugwitz K-L, Moretti A, Lam J et al. Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature433(7026), 647–653 (2005).
  • Matsuura K, Nagai T, Nishigaki N et al. Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. J. Biol. Chem.279(12), 11384–11391 (2004).
  • Hierlihy AM, Seale P, Lobe CG, Rudnicki MA, Megeney LA. The post-natal heart contains a myocardial stem cell population. FEBS Lett.530(1–3), 239–243 (2002).
  • Martin CM, Meeson AP, Robertson SM et al. Persistent expression of the ATP-binding cassette transporter, ABCG2, identifies cardiac SP cells in the developing and adult heart. Dev. Biol.265(1), 262–275 (2004).
  • Smith RR, Barile L, Messina E, Marban E. Stem cells in the heart: what’s the buzz all about? Part I: preclinical considerations. Heart Rhythm5, 749–757 (2008).
  • Smith RR, Barile L, Messina E, Marban E. Stem cells in the heart: what’s the buzz all about? Part 2: arrhythmic risks and clinical studies. Heart Rhythm5, 880–887 (2008).
  • Oh H, Bradfute SB, Gallardo TD et al. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc. Natl Acad. Sci. USA100(21), 12313–12318 (2003).
  • Li Z, Lee A, Huang M et al. Imaging Survival and function of transplanted cardiac resident stem cells. J. Am. Coll. Cardiol.53(14), 1229–1240 (2009).
  • Tomita S, Li R-K, Weisel RD et al. Autologous transplantation of bone marrow cells improves damaged heart function. Circulation100(90002), II247–II256 (1999).
  • Makino S, Fukuda K, Miyoshi S et al. Cardiomyocytes can be generated from marrow stromal cells in vitro. J. Clin. Invest.103(5), 697–705 (1999).
  • Mazhari R, Hare JM. Advances in cell-based therapy for structural heart Disease. Prog. Cardiovasc. Dis.49(6), 387–395 (2007).
  • Mazhari R, Hare JM. Mechanisms of action of mesenchymal stem cells in cardiac repair: potential influences on the cardiac stem cell niche. Nat. Clin. Pract. Cardiovasc. Med.4 (Suppl. 1), S21–S26 (2007).
  • Schuleri KH, Amado LC, Boyle AJ et al. Early improvement in cardiac tissue perfusion due to mesenchymal stem cells. Am. J. Physiol. Heart Circ. Physiol.294(5), H2002–H2011 (2008).
  • Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation105(1), 93–98 (2002).
  • Liechty K, MacKenzie T, Shaaban A et al. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation ater in utero transplantation in sheep. Nat. Med.6, 1282–1286 (2000).
  • Boheler K, Czyz J, Tweedie D, Yang H-T, Anisimov SV, Wobus AM. Differentiation of pluripotent embryonic stem cells into cardiomyocytes. Circ. Res.91, 189–201 (2002).
  • Swijnenburg R-J, Tanaka M, Vogel H et al. Embryonic stem cell immunogenicity increases upon differentiation after transplantation into ischemic myocardium. Circulation112(Suppl. 9), I166–I172 (2005).
  • Singla DK, Hacker TA, Ma L et al. Transplantation of embryonic stem cells into the infarcted mouse heart: formation of multiple cell types. J. Mol. Cell. Cardiol.40(1), 195–200 (2006).
  • Solter D. From teratomacrcinomas to embryonic stem cells and beyond: a history of embryonic stem cell research. Nat. Rev. Genet.7(4), 319–327 (2006).
  • Tomescot A, Leschik J, Bellamy V et al. Differentiation in vivo of cardiac committed human embryonic stem cells in postmyocardial infarcted rats. Stem Cells25(9), 2200–2205 (2007).
  • Behfar A, Faustino RS, Arrell DK, Dzeja PP, Perez-Terzic C, Terzic A. Guided stem cell cardiopoiesis: discovery and translation. J. Mol. Cell. Cardiol.45(4), 523–529 (2008).
  • Behfar A, Perez-Terzic C, Faustino RS et al. Cardiopoietic programming of embryonic stem cells for tumor-free heart repair. J. Exp. Med.204(2), 405–420 (2007).
  • Kucia M, Halasa M, Wysoczynski M et al. Morphological and molecular characterization of a novel population of CXCR4+ SSEA-4+ ct-4+ very small embyonic-like cells purified from human cord blood: preliminary report. Leukemia21, 297–303 (2007).
  • Kucia M, Reca R, Campbell F et al. A population of very small embryonic-like (VSEL) CXCR4+SSEA-1+Oct-4+ stem cells identified in adult bone marrow. Leukemia20, 857–869 (2006).
  • Zuba-Surma EK, Kucia M, Abdel-Latif A et al. Morphological characterization of very small embryonic-like stem cells (VSELs) by ImageStream system analysis. J. Cell. Mol. Med.12(1), 292–303 (2008).
  • Zuba-Surma EK, Kucia M, Dawn B, Guo Y, Ratajczak MZ, Bolli R. Bone marrow-derived pluripotent very small embryonic-like stem cells (VSELs) are mobilized after acute myocardial infarction. J. Mol. Cell. Cardiol.44(5), 865–873 (2008).
  • Dawn B, Tiwari S, Kucia MJ et al. Transplantation of bone marrow-derived very small embryonic-like stem cells attenuates left ventricular dysfunction and remodeling after myocardial infarction. Stem Cells26(6), 1646–1655 (2008).
  • Kim B-O, Tian H, Prasongsukarn K et al. Cell transplantation improves ventricular function after a myocardial infarction: a preclinical study of human unrestricted somatic stem cells in a porcine model. Circulation112(Suppl. 9), I-96–I-104 (2005).
  • Wu KH, Zhou B, Yu CT et al. Therapeutic potential of human umbilical cord derived stem cells in a rat myocardial infarction model. Ann. Thorac. Surg.83(4), 1491–1498 (2007).
  • Chiavegato A, Bollini S, Pozzobon M et al. Human amniotic fluid-derived stem cells are rejected after transplantation in the myocardium of normal, ischemic, immuno-suppressed or immuno-deficient rat. J. Mol. Cell. Cardiol.42(4), 746–759 (2007).
  • Moelker AD, Baks T, Wever KMAM et al. Intracoronary delivery of umbilical cord blood derived unrestricted somatic stem cells is not suitable to improve LV function after myocardial infarction in swine. J. Mol. Cell. Cardiol.42(4), 735–745 (2007).
  • Zhou R, Thomas DH, Qiao H et al. In vivo detection of stem cells grafted in infarcted rat myocardium. J. Nucl. Med.46(5), 816–822 (2005).
  • Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell126, 663–676 (2006).
  • Park I-H, Zhao R, West JA et al. Reprogramming of human somatic cells to pluripotency with defined factors. Nature451, 141–146 (2008).
  • Takahashi K, Tanabe K, Ohnuki M et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell131(5), 861–872 (2007).
  • Yu J, Vodyanik MA, Smuga-Otto K et al. Induced pluripotent stem cell lines derived from human somatic cells. Science318(5858), 1917–1920 (2007).
  • Mauritz C, Schwanke K, Reppel M et al. Generation of functional murine Cardiac myocytes from induced pluripotent stem cells. Circulation118, 507–517 (2008).
  • Narazaki G, Uosaki H, Teranishi M et al. Directed and systematic differentiation of cardiovascular cells from mouse induced pluripotent stem cells. Circulation118, 498–506 (2008).
  • Nelson TJ, Martinez-Fernandez A, Yamada S, Perez-Terzic C, Ikeda Y, Terzic A. Repair of acute myocardial infarction by human stemness factors induced pluripotent stem cells. Circulation120(5), 408–416 (2009).
  • Schenke-Layland K, Rhodes KE, Angelis E et al. Reprogrammed mouse fibroblasts differentiate into cells of the cardiovascular and hematopoietic lineages. Stem Cells26(6), 1537–1546 (2008).
  • Zhang J, Wilson GF, Soerens AG et al. Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ. Res.104(4), e30–e41 (2009).
  • Martinez-Fernandez A, Nelson TJ, Yamada S et al. iPS programmed without c-MYC yield proficient cardiogenesis for functional heart chimerism. Circ. Res.105(7), 648–656 (2009).
  • Blin G, Nury D, Stefanovic S et al. A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates. J. Clin. Invest.120(4), 1125–1139 (2010).
  • Kuethe F, Richartz BM, Sayer HG et al. Lack of regeneration of myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans with large anterior myocardial infarctions. Int. J. Cardiol.97(1), 123–127 (2004).
  • Hill JM, Syed MA, Arai AE et al. Outcomes and risks of granulocyte colony-stimulating factor in patients with coronary artery disease. J. Am. Coll. Cardiol.46(9), 1643–1648 (2005).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.