Journal of Cardiovascular Translational Research

, Volume 1, Issue 3, pp 207–216 | Cite as

Cardiac Stem Cell Therapy and Arrhythmogenicity: Prometheus and the arrows of Apollo and Artemis

  • Alexander R. Lyon
  • Sian E. Harding
  • Nicholas S. Peters
Article

Abstract

Cardiac cell therapy is an expanding scientific field which is yielding new insights into the pathogenesis of cardiac disease and offers new therapeutic strategies. Inherent to both these areas of research are the electrical properties of individual cells, the electrical interplay between cardiomyocytes, and their roles in arrhythmogenesis. This review discusses the potential mechanisms by which various candidate cells for cardiac therapy may modulate the ventricular arrhythmic substrate and highlights the data and lessons learnt from the clinical cardiac cell therapy trials published to date. Pro- and antiarrhythmic mechanistic factors are discussed, and the importance of their consideration in the design of any future clinical cell therapy trials.

Keywords

Stem Cells Arrhythmia Myocardium 

Notes

Conflicts of interest

None

References

  1. 1.
    Lyon, A., & Harding, S. (2007). The potential of cardiac stem cell therapy for heart failure. Current Opinion in Pharmacology, 7(2), 164–170 April.PubMedCrossRefGoogle Scholar
  2. 2.
    Dimmeler, S., Zeiher, A. M., & Schneider, M. D. (2005). Unchain my heart: the scientific foundations of cardiac repair. Journal of Clinical Investigation, 115(3), 572–583 March 1.PubMedGoogle Scholar
  3. 3.
    Wollert, K. C., & Drexler, H. (2005). Mesenchymal stem cells for myocardial infarction: promises and pitfalls. Circulation, 112(2), 151–153 July 12.PubMedCrossRefGoogle Scholar
  4. 4.
    Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm S. ACC/AHA/ESC (2006). 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing committee to develop guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death). Journal of the American College of Cardiology, 48(5), e247–e346 September 5.CrossRefGoogle Scholar
  5. 5.
    Dargie, H. J. (2001). Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet, 357, 1385–1390 May 5.PubMedCrossRefGoogle Scholar
  6. 6.
    Moss, A. J., Zareba, W., Hall, W. J., et al. (2002). Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. The New England Journal of Medicine, 346, 877–883 March 21.PubMedCrossRefGoogle Scholar
  7. 7.
    Laflamme, M. A., & Murry, C. E. (2005). Regenerating the heart. Nature Biotechnology, 23(7), 845–856 July.PubMedCrossRefGoogle Scholar
  8. 8.
    van Laake, L. W., Hassink, R., Doevendans, P. A., & Mummery, C. (2006). Heart repair and stem cells. Journal Of Physiology (London), 577(2), 467–478 December 1.CrossRefGoogle Scholar
  9. 9.
    Berry, M. F., Engler, A. J., Woo, Y. J., et al. (2006). Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance. American Journal of Physiology. Heart and Circulatory Physiology, 290(6), H2196–H2203 June 1.PubMedCrossRefGoogle Scholar
  10. 10.
    Toma, C., Pittenger, M. F., Cahill, K. S., Byrne, B. J., & Kessler, P. D. (2002). Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation, 105(1), 93–98 January 1.PubMedCrossRefGoogle Scholar
  11. 11.
    Meyer, G. P., Wollert, K. C., Lotz, J., et al. (2006). 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, 113(10), 1287–1294 March 14.PubMedCrossRefGoogle Scholar
  12. 12.
    Schachinger, V., Erbs, S., Elsasser, A., et al. (2006). Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. The New England Journal of Medicine, 355(12), 1210–1221 September 21.PubMedCrossRefGoogle Scholar
  13. 13.
    Janssens, S., Dubois, C., Bogaert, J., et al. (2006). Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. The Lancet, 367(9505), 113–121.CrossRefGoogle Scholar
  14. 14.
    Lunde, K., Solheim, S., Aakhus, S., et al. (2006). Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. The New England Journal of Medicine, 355(12), 1199–1209 September 21.PubMedCrossRefGoogle Scholar
  15. 15.
    Assmus, B., Honold, J., Schachinger, V., et al. (2006). Transcoronary transplantation of progenitor cells after myocardial infarction. The New England Journal of Medicine, 355(12), 1222–1232 September 21.PubMedCrossRefGoogle Scholar
  16. 16.
    Perin, E. C., Dohmann, H. F., Borojevic, R., et al. (2003). Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation, 107(18), 2294–2302 May 13.PubMedCrossRefGoogle Scholar
  17. 17.
    Orlic, D., Kajstura, J., Chimenti, S., et al. (2001). Bone marrow cells regenerate infarcted myocardium. Nature, 410(6829), 701–705 April 5.PubMedCrossRefGoogle Scholar
  18. 18.
    Rota, M., Kajstura, J., Hosoda, T., et al. (2007). Bone marrow cells adopt the cardiomyogenic fate in vivo. Proceedings of the National Academy of Sciences of the United States of America, 104(45), 17783–1778 November 6.PubMedCrossRefGoogle Scholar
  19. 19.
    Murry, C. E., Soonpaa, M. H., Reinecke, H., et al. (2004). Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature, 428(6983), 664–668 April 8.PubMedCrossRefGoogle Scholar
  20. 20.
    Balsam, L. B., Wagers, A. J., Christensen, J. L., Kofidis, T., Weissman, I. L., & Robbins, R. C. (2004). Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature, 428(6983), 668–673 April 8.PubMedCrossRefGoogle Scholar
  21. 21.
    Lehrke, S., Mazhari, R., Durand, D. J., et al. (2006). Aging impairs the beneficial effect of granulocyte colony-stimulating factor and stem cell factor on post-myocardial infarction remodeling. Circulation Research, 99(5), 553–560 September 1.PubMedCrossRefGoogle Scholar
  22. 22.
    Heeschen, C., Lehmann, R., Honold, J., et al. (2004). Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease. Circulation, 109(13), 1615–1622 April 6.PubMedCrossRefGoogle Scholar
  23. 23.
    Walter, D. H., Haendeler, J., Reinhold, J., et al. (2005). Impaired CXCR4 signaling contributes to the reduced neovascularization capacity of endothelial progenitor cells from patients with coronary artery disease. Circulation Research, 97(11), 1142–1151 November 25.PubMedCrossRefGoogle Scholar
  24. 24.
    Fazel, S., Cimini, M., Chen, L., et al. (2006). Cardioprotective c-kit+ cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines. Journal of Clinical Investigation, 116(7), 1865–1877 July 3.PubMedCrossRefGoogle Scholar
  25. 25.
    Dohmann, H. F. R., Perin, E. C., Takiya, C. M., et al. (2005). Transendocardial autologous bone marrow mononuclear cell injection in ischemic heart failure: postmortem anatomicopathologic and immunohistochemical findings. Circulation, 112(4), 521–526 July 26.PubMedCrossRefGoogle Scholar
  26. 26.
    Mollmann, H., Nef, H. M., Kostin, S., et al. (2006). Bone marrow-derived cells contribute to infarct remodelling. Cardiovascular Research, 71(4), 661–671 September 1.PubMedCrossRefGoogle Scholar
  27. 27.
    Drexler, H., Meyer, G. P., & Wollert, K. C. (2006). Bone-marrow-derived cell transfer after ST-elevation myocardial infarction: lessons from the BOOST trial. Nature Clinical Practice Cardiovascular Medicine, 3(Suppl 1), S65–S68 March.PubMedCrossRefGoogle Scholar
  28. 28.
    Valina, C., Pinkernell, K., Song, Y. H., et al. (2007). Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction. European Heart Journal, 28(21), 2667–2677 November 1.PubMedCrossRefGoogle Scholar
  29. 29.
    Hoogduijn, M. J., Crop, M. J., Peeters, A. M., et al. (2007). Human heart, spleen, and perirenal fat-derived mesenchymal stem cells have immunomodulatory capacities. Stem Cells Dev, 16(4), 597–604 August.PubMedCrossRefGoogle Scholar
  30. 30.
    Beltrami, A. P., Barlucchi, L., Torella, D., et al. (2003). Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell, 114(6), 763–776 September 19.PubMedCrossRefGoogle Scholar
  31. 31.
    Linke, A., Muller, P., Nurzynska, D., et al. (2005). Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. Proceedings of the National Academy of Sciences, 102(25), 8966–8971 June 21.CrossRefGoogle Scholar
  32. 32.
    Laugwitz, K. L., Moretti, A., Lam, J., et al. (2005). Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature, 433(7026), 647–653 February 10.PubMedCrossRefGoogle Scholar
  33. 33.
    Oh, H., Bradfute, S. B., Gallardo, T. D., et al. (2003). Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proceedings of the National Academy of Sciences, 100(21), 12313–12318 October 14.CrossRefGoogle Scholar
  34. 34.
    Kehat, I., Kenyagin-Karsenti, D., Snir, M., et al. (2001). Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. The Journal of Clinical Investigation, 108, 407–414 August.PubMedGoogle Scholar
  35. 35.
    Laflamme, M. A., Gold, J., Xu, C., et al. (2005). Formation of human myocardium in the rat heart from human embryonic stem cells. The American Journal of Pathology, 167(3), 663–671 September.PubMedGoogle Scholar
  36. 36.
    Caspi, O., Huber, I., Kehat, I., et al. (2007). Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. Journal of the American College of Cardiology, 50(19), 1884–1893 November 6.PubMedCrossRefGoogle Scholar
  37. 37.
    He, J. Q., Ma, Y., Lee, Y., Thomson, J. A., & Kamp, T. J. (2003). Human embryonic stem cells develop into multiple types of cardiac myocytes: action potential characterization. Circulation Research, 93, 32–39.PubMedCrossRefGoogle Scholar
  38. 38.
    Mummery, C., Ward-van Oostwaard, D., Doevendans, P., et al. (2003). Differentiation of human embryonic stem cells to cardiomyocytes: role of coculture with visceral endoderm-like cells. Circulation, 107(21), 2733–2740 June 3.PubMedCrossRefGoogle Scholar
  39. 39.
    Takahashi, K., Tanabe, K., Ohnuki, M., et al. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131(5), 861–872 November 30.PubMedCrossRefGoogle Scholar
  40. 40.
    Yu, J., Vodyanik, M. A., Smuga-Otto, K., et al. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science, 318(5858), 1917–1920 December 21.PubMedCrossRefGoogle Scholar
  41. 41.
    Kleber, A. G., & Rudy, Y. (2004). Basic mechanisms of cardiac impulse propagation and associated arrhythmias. Physiological Reviews, 84(2), 431–488 April.PubMedCrossRefGoogle Scholar
  42. 42.
    Heubach, J. F., Graf, E. M., Leutheuser, J., et al. (2004). Electrophysiological properties of human mesenchymal stem cells. Journal of Physiology (London), 554(3), 659–672 February 1.CrossRefGoogle Scholar
  43. 43.
    Bunch, T. J., Mahapatra, S., Bruce, G. K., et al. (2006). Impact of transforming growth factor-{beta}1 on atrioventricular node conduction modification by injected autologous fibroblasts in the canine Heart. Circulation, 113(21), 2485–2494.PubMedCrossRefGoogle Scholar
  44. 44.
    Peters, N. S. (2006). Gap junctions: clarifying the complexities of connexins and conduction. Circulation Research, 99(11), 1156–1158 November 24.PubMedCrossRefGoogle Scholar
  45. 45.
    Akar, F. G., Nass, R. D., Hahn, S., et al. (2007). Dynamic changes in conduction velocity and gap junction properties during development of pacing-induced heart failure. American Journal of Physiology. Heart and Circulatory Physiology, 293(2), H1223–H1230 August.PubMedCrossRefGoogle Scholar
  46. 46.
    Akar, F. G., Spragg, D. D., Tunin, R. S., Kass, D. A., & Tomaselli, G. F. (2004). Mechanisms underlying conduction slowing and arrhythmogenesis in nonischemic dilated cardiomyopathy. Circulation Research, 95(7), 717–725 October 1.PubMedCrossRefGoogle Scholar
  47. 47.
    Cabo, C., Yao, J., Boyden, P. A., et al. (2006). Heterogeneous gap junction remodeling in reentrant circuits in the epicardial border zone of the healing canine infarct. Cardiovascular Research, 72(2), 241–249 November 1.PubMedCrossRefGoogle Scholar
  48. 48.
    Peters, N. S., Green, C. R., Poole-Wilson, P. A., & Severs, N. J. (1993). Reduced content of connexin43 gap junctions in ventricular myocardium from hypertrophied and ischemic human hearts. Circulation, 88(3), 864–875 September.PubMedGoogle Scholar
  49. 49.
    Peters, N. S., Coromilas, J., Severs, N. J., & Wit, A. L. (1997). Disturbed connexin43 gap junction distribution correlates with the location of reentrant circuits in the epicardial border zone of healing canine infarcts that cause ventricular tachycardia. Circulation, 95(4), 988–996 February 18.PubMedGoogle Scholar
  50. 50.
    Smith, J. H., Green, C. R., Peters, N. S., Rothery, S., & Severs, N. J. (1991). Altered patterns of gap junction distribution in ischemic heart disease. An immunohistochemical study of human myocardium using laser scanning confocal microscopy. The American Journal of Pathology, 139(4), 801–821 October.PubMedGoogle Scholar
  51. 51.
    Hagege, A. A., Marolleau, J. P., Vilquin, J. T., et al. (2006). Skeletal myoblast transplantation in ischemic heart failure: long-term follow-up of the first phase I cohort of patients. Circulation, 114(1_suppl), I–108–I-113 July 4.CrossRefGoogle Scholar
  52. 52.
    Al, A. N., Carrion, C., Ghostine, S., et al. (2003). Long-term (1 year) functional and histological results of autologous skeletal muscle cells transplantation in rat. Cardiovascular Research, 58(1), 142–148 April 1.CrossRefGoogle Scholar
  53. 53.
    Leobon, B., Garcin, I., Menasche, P., Vilquin, J. T., Audinat, E., & Charpak, S. (2003). Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host. Proceedings of the National Academy of Sciences of the United States of America, 100(13), 7808–7811 June 24.PubMedCrossRefGoogle Scholar
  54. 54.
    Reinecke, H., MacDonald, G. H., Hauschka, S. D., & Murry, C. E. (2000). Electromechanical coupling between skeletal and cardiac muscle. Implications for infarct repair. The Journal of Cell Biology, 149(3), 731–740 May 1.PubMedCrossRefGoogle Scholar
  55. 55.
    Fouts, K., Fernandes, B., Mal, N., Liu, J., & Laurita, K. R. (2006). Electrophysiological consequence of skeletal myoblast transplantation in normal and infarcted canine myocardium. Heart Rhythm, 3(4), 452–461 April.PubMedCrossRefGoogle Scholar
  56. 56.
    Scorsin, M., Hagege, A., Vilquin, J. T., et al. (2000). Comparison of the effects of fetal cardiomyocyte and skeletal myoblast transplantation on postinfarction left ventricular function. Journal of Thoracic and Cardiovascular Surgery, 119(6), 1169–1175 June.PubMedCrossRefGoogle Scholar
  57. 57.
    Hagege, A. A., Carrion, C., Menasche, P., et al. (2003). Viability and differentiation of autologous skeletal myoblast grafts in ischaemic cardiomyopathy. The Lancet, 361(9356), 491–492 February 8.CrossRefGoogle Scholar
  58. 58.
    Tolmachov, O., Ma, Y. L., Themis, M., et al. (2006). Overexpression of connexin 43 using a retroviral vector improves electrical coupling of skeletal myoblasts with cardiac myocytes in vitro. BMC Cardiovasc Disord, 6, 25.PubMedCrossRefGoogle Scholar
  59. 59.
    Stagg, M. A., Coppen, S. R., Suzuki, K., et al. (2006). Evaluation of frequency, type, and function of gap junctions between skeletal myoblasts overexpressing connexin43 and cardiomyocytes: relevance to cell transplantation. FASEB J, 20(6), 744–746 05-5088fje, January 27.PubMedGoogle Scholar
  60. 60.
    Abraham, M. R., Henrikson, C. A., Tung, L., et al. (2005). Antiarrhythmic engineering of skeletal myoblasts for cardiac transplantation. Circulation Research, 97(2), 159–167 July 22.PubMedCrossRefGoogle Scholar
  61. 61.
    Roell, W., Lewalter, T., Sasse, P., et al. (2007). Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia. Nature, 450(7171), 819–824 December 6.PubMedCrossRefGoogle Scholar
  62. 62.
    Caspi, O., Huber, I., Kehat, I., et al. (2007). Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. Journal of the American College of Cardiology, 50(19), 1884–1893 November 6.PubMedCrossRefGoogle Scholar
  63. 63.
    Kehat, I., Khimovich, L., Caspi, O., et al. (2004). Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nature Biotechnology, 22(10), 1282–1289 October.PubMedCrossRefGoogle Scholar
  64. 64.
    Chang, M. G., Tung, L., Sekar, R. B., et al. (2006). Proarrhythmic potential of mesenchymal stem cell transplantation revealed in an in vitro coculture model. Circulation, 113(15), 1832–1841 April 18.PubMedCrossRefGoogle Scholar
  65. 65.
    Guan, K., Wagner, S., Unsold, B., et al. (2007). Generation of functional cardiomyocytes from adult mouse spermatogonial stem cells. Circulation Research, 100(11), 1615–1625 June 8.PubMedCrossRefGoogle Scholar
  66. 66.
    Muller-Borer, B. J., Cascio, W. E., Esch, G. L., et al. (2007). Mechanisms controlling the acquisition of a cardiac phenotype by liver stem cells. Proceedings of the National Academy of Sciences, 104(10), 3877–3882 March 6.CrossRefGoogle Scholar
  67. 67.
    Giepmans, B. N. G. (2004). Gap junctions and connexin-interacting proteins. Cardiovascular Research, 62(2), 233–245 May 1.PubMedCrossRefGoogle Scholar
  68. 68.
    Akar, F. G., & Rosenbaum, D. S. (2003). Transmural electrophysiological heterogeneities underlying arrhythmogenesis in heart failure. Circulation Research, 93(7), 638–645 October 3.PubMedCrossRefGoogle Scholar
  69. 69.
    Salama, G., & Choi, B. R. (2007). Imaging ventricular fibrillation. Journal of Electrocardiology, 40(6 Suppl), S56–S61 November.PubMedCrossRefGoogle Scholar
  70. 70.
    Iannaccone, S. T., Li, K. X., & Sperelakis, N. (1987). Transmembrane electrical characteristics of cultured human skeletal muscle cells. Journal of Cellular Physiology, 133(2), 409–413 November.PubMedCrossRefGoogle Scholar
  71. 71.
    Harding, S. E., Ali, N. N., Brito-Martins, M., & Gorelik, J. (2007). The human embryonic stem cell-derived cardiomyocyte as a pharmacological model. Pharmacology & Therapeutics, 113(2), 341–353 February.CrossRefGoogle Scholar
  72. 72.
    Orlic, D., Kajstura, J., Chimenti, S., et al. (2001). Bone marrow cells regenerate infarcted myocardium. Nature, 410, 701–705 April 5.PubMedCrossRefGoogle Scholar
  73. 73.
    Caspi, O., Lesman, A., Basevitch, Y., et al. (2007). Tissue engineering of vascularized cardiac muscle from human embryonic stem cells. Circulation Research, 100(2), 263–272 February 2.PubMedCrossRefGoogle Scholar
  74. 74.
    Kehat, I., Kenyagin-Karsenti, D., Snir, M., et al. (2001). Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. The Journal Of Clinical Investigation, 108, 407–414 August.PubMedGoogle Scholar
  75. 75.
    Satin, J., Kehat, I., Caspi, O., et al. (2004). Mechanism of spontaneous excitability in human embryonic stem cell derived cardiomyocytes. Journal of Physiology, 559(Pt 2), 479–496 September 1.PubMedCrossRefGoogle Scholar
  76. 76.
    Yanagi, K., Takano, M., Narazaki, G., et al. (2007). Hyperpolarization-activated cyclic nucleotide-gated channels and T-type calcium channels confer automaticity of embryonic stem cell-derived cardiomyocytes. Stem Cells, 25(11), 2712–2719 November.PubMedCrossRefGoogle Scholar
  77. 77.
    Yang, H. T., Tweedie, D., Wang, S., et al. (2002). The ryanodine receptor modulates the spontaneous beating rate of cardiomyocytes during development. Proceedings of the National Academy of Sciences of the United States of America, 99(14), 9225–9230 July 9.PubMedCrossRefGoogle Scholar
  78. 78.
    Viatchenko-Karpinski, S., Fleischmann, B. K., Liu, Q., et al. (1999). Intracellular Ca2+ oscillations drive spontaneous contractions in cardiomyocytes during early development. Proceedings of the National Academy of Sciences of the United States of America, 96(14), 8259–8264 July 6.PubMedCrossRefGoogle Scholar
  79. 79.
    Xue, T., Cho, H. C., Akar, F. G., et al. (2005). Functional integration of electrically active cardiac derivatives from genetically engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes: insights into the development of cell-based pacemakers. Circulation, 111(1), 11–20 January 4.PubMedCrossRefGoogle Scholar
  80. 80.
    Grossman, P. M., Han, Z., Palasis, M., Barry, J. J., & Lederman, R. J. (2002). Incomplete retention after direct myocardial injection. Catheterization and Cardiovascular Interventions, 55(3), 392–397 March.PubMedCrossRefGoogle Scholar
  81. 81.
    Hofmann, M., Wollert, K. C., Meyer, G. P., et al. (2005). Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation, 111(17), 2198–2202 May 3.PubMedCrossRefGoogle Scholar
  82. 82.
    Vulliet, P. R., Greeley, M., Halloran, S. M., MacDonald, K. A., & Kittleson, M. D. (2004). Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet, 363(9411), 783–784 March 6.PubMedCrossRefGoogle Scholar
  83. 83.
    Menasche, P., Hagege, A. A., Vilquin, J. T., et al. (2003). Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. Journal of the American College of Cardiology, 41(7), 1078–1083 April 2.PubMedCrossRefGoogle Scholar
  84. 84.
    Smits, P. C., van Geuns, R. J., Poldermans, D., et al. (2003). Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up. Journal of the American College of Cardiology, 42(12), 2063–2069 December 17.PubMedCrossRefGoogle Scholar
  85. 85.
    Hagege, A. A., Marolleau, J. P., Vilquin, J. T., et al. (2006). Skeletal myoblast transplantation in ischemic heart failure: long-term follow-up of the first phase I cohort of patients. Circulation, 114(1 Suppl), I108–I113 July 4.PubMedGoogle Scholar
  86. 86.
    Siminiak, T., Fiszer, D., Jerzykowska, O., et al. (2005). Percutaneous trans-coronary-venous transplantation of autologous skeletal myoblasts in the treatment of post-infarction myocardial contractility impairment: the POZNAN trial. European Heart Journal, 26(12), 1188–1195 June 2.PubMedCrossRefGoogle Scholar
  87. 87.
    Dib, N., Michler, R. E., Pagani, F. D., et al. (2005). Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: four-year follow-up. Circulation, 112(12), 1748–1755 September 20.PubMedCrossRefGoogle Scholar
  88. 88.
    Menasche, P., Alfieri, O., Janssens, S., et al. (2008). The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial: first randomized placebo-controlled study of myoblast transplantation. Circulation, 117(9), 1189–1200 March 4.PubMedCrossRefGoogle Scholar
  89. 89.
    Fukushima, S., Varela-Carver, A., Coppen, S. R., et al. (2007). Direct intramyocardial but not intracoronary injection of bone marrow cells induces ventricular arrhythmias in a rat chronic ischemic heart failure model. Circulation, 115(17), 2254–2261 May 1.PubMedCrossRefGoogle Scholar
  90. 90.
    Tse, H. F., Thambar, S., Kwong, Y. L., et al. (2007). Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial). European Heart Journal, 28(24), 2998–3005 ehm485, November 5.PubMedCrossRefGoogle Scholar
  91. 91.
    de la Fuente, L. M., Stertzer, S. H., Argentieri, J., et al. (2007). Transendocardial autologous bone marrow in chronic myocardial infarction using a helical needle catheter: 1-year follow-up in an open-label, nonrandomized, single-center pilot study (the TABMMI study). The American Heart Journal, 154(1), 79–77 July.Google Scholar
  92. 92.
    Mills, W. R., Mal, N., Kiedrowski, M. J., et al. (2007). Stem cell therapy enhances electrical viability in myocardial infarction. Journal of Molecular and Cellular Cardiology, 42(2), 304–314 February.PubMedCrossRefGoogle Scholar
  93. 93.
    Roell, W., Lewalter, T., Sasse, P., et al. (2007). Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia. Nature, 450(7171), 819–824 December 6.PubMedCrossRefGoogle Scholar
  94. 94.
    Katritsis, D. G., Sotiropoulou, P., Giazitzoglou, E., Karvouni, E., & Papamichail, M. (2007). Electrophysiological effects of intracoronary transplantation of autologous mesenchymal and endothelial progenitor cells. Europace, 9(3), 167–171 March.PubMedCrossRefGoogle Scholar
  95. 95.
    Jawad, H., Ali, N. N., Lyon, A. R., Chen, Q. Z., Harding, S. E., & Boccaccini, A. R. (2007). Myocardial tissue engineering: a review. Journal of Tissue Engineering and Regenerative Medicine, 1(5), 327–342 September.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Alexander R. Lyon
    • 1
  • Sian E. Harding
    • 1
  • Nicholas S. Peters
    • 1
  1. 1.National Heart and Lung Institute, Faculty of MedicineImperial CollegeLondonUK

Personalised recommendations