Stem Cell Therapy for Chronic Myocardial Infarction

Article

Abstract

Although recent advances for the treatment of myocardial infarction have dramatically increased the rate of survival after the ischemic event, this has also led to a rise in the number of chronic patients, making the finding of a suitable therapy a compulsory subject for modern medicine. Over the last decade, stem cells have been a promise for the cure of several diseases not only due to their plasticity but also to their capacity to act in a paracrine manner and influence the affected tissue, prompting the launching of several clinical trials. In spite of the knowledge already acquired, stem cell application to chronically infarcted hearts has been much less approached than its acute counterpart. Through this review, we will focus in stem cell therapy in animal models of chronic myocardial infarction: cell types employed, functional results, mechanisms analyzed, and questions raised.

Keywords

Chronic Myocardial Infarction Stem Cell Animal Models 

Reference

  1. 1.
    Adamopoulos, S., Parissis, J. T., & Kremastinos, D. T. (2001). A glossary of circulating cytokines in chronic heart failure. European Journal of Heart Failure, 3, 517–526.CrossRefPubMedGoogle Scholar
  2. 2.
    Agbulut, O., Mazo, M., Bressolle, C., Gutierrez, M., Azarnoush, K., Sabbah, L., et al. (2006). Can bone marrow-derived multipotent adult progenitor cells regenerate infarcted myocardium? Cardiovascular Research, 72, 175–183.CrossRefPubMedGoogle Scholar
  3. 3.
    Armstrong, P. W., Granger, C. B., Adams, P. X., Hamm, C., Holmes, D., Jr., O'Neill, W. W., et al. (2007). Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: A randomized controlled trial. JAMA, 297, 43–51.CrossRefPubMedGoogle Scholar
  4. 4.
    Bai, X., Pinkernell, K., Song, Y. H., Nabzdyk, C., Reiser, J., & Alt, E. (2007). Genetically selected stem cells from human adipose tissue express cardiac markers. Biochemical and Biophysical Research Communications, 353, 665–671.CrossRefPubMedGoogle Scholar
  5. 5.
    Behfar, A., Faustino, R. S., Arrell, D. K., Dzeja, P. P., Perez-Terzic, C., & Terzic, A. (2008). Guided stem cell cardiopoiesis: Discovery and translation. Journal of Molecular and Cellular Cardiology, 45, 523–529.CrossRefPubMedGoogle Scholar
  6. 6.
    Bonaros, N., Rauf, R., Werner, E., Schlechta, B., Rohde, E., Kocher, A., et al. (2008). Neoangiogenesis after combined transplantation of skeletal myoblasts and angiopoietic progenitors leads to increased cell engraftment and lower apoptosis rates in ischemic heart failure. Interact Cardiovasc Thorac Surg, 7, 249–255.CrossRefPubMedGoogle Scholar
  7. 7.
    Bonaros, N., Rauf, R., Wolf, D., Margreiter, E., Tzankov, A., Schlechta, B., et al. (2006). Combined transplantation of skeletal myoblasts and angiopoietic progenitor cells reduces infarct size and apoptosis and improves cardiac function in chronic ischemic heart failure. Journal of Thoracic and Cardiovascular Surgery, 132, 1321–1328.CrossRefPubMedGoogle Scholar
  8. 8.
    Breitbach, M., Bostani, T., Roell, W., Xia, Y., Dewald, O., Nygren, J. M., et al. (2007). Potential risks of bone marrow cell transplantation into infarcted hearts. Blood, 110, 1362–1369.CrossRefPubMedGoogle Scholar
  9. 9.
    Bujak, M. & Frangogiannis, N. G. (2007). The role of TGF-beta signaling in myocardial infarction and cardiac remodeling. Cardiovascular Research, 74, 184–195.CrossRefPubMedGoogle Scholar
  10. 10.
    Caspi, O., Huber, I., Kehat, I., Habib, M., Arbel, G., Gepstein, A., 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, 1884–1893.CrossRefPubMedGoogle Scholar
  11. 11.
    Cleutjens, J. P., Kandala, J. C., Guarda, E., Guntaka, R. V., & Weber, K. T. (1995). Regulation of collagen degradation in the rat myocardium after infarction. Journal of Molecular and Cellular Cardiology, 27, 1281–1292.CrossRefPubMedGoogle Scholar
  12. 12.
    Chang, S. A., Lee, E. J., Kang, H. J., Zhang, S. Y., Kim, J. H., Li, L., et al. (2008). Impact of myocardial infarct proteins and oscillating pressure on the differentiation of mesenchymal stem cells: Effect of acute myocardial infarction on stem cell differentiation. Stem Cells, 26, 1901–1912.CrossRefPubMedGoogle Scholar
  13. 13.
    Desmouliere, A., Chaponnier, C., & Gabbiani, G. (2005). Tissue repair, contraction, and the myofibroblast. Wound Repair and Regeneration, 13, 7–12.CrossRefPubMedGoogle Scholar
  14. 14.
    Deten, A., Volz, H. C., Briest, W., & Zimmer, H. G. (2002). Cardiac cytokine expression is upregulated in the acute phase after myocardial infarction. Experimental studies in rats. Cardiovascular Research, 55, 329–340.CrossRefPubMedGoogle Scholar
  15. 15.
    Ertl, G. & Frantz, S. (2005). Healing after myocardial infarction. Cardiovascular Research, 66, 22–32.CrossRefPubMedGoogle Scholar
  16. 16.
    Farahmand, P., Lai, T. Y., Weisel, R. D., Fazel, S., Yau, T., Menasche, P., et al. (2008). Skeletal myoblasts preserve remote matrix architecture and global function when implanted early or late after coronary ligation into infarcted or remote myocardium. Circulation, 118, S130–137.CrossRefPubMedGoogle Scholar
  17. 17.
    Fishbein, M. C., Maclean, D., & Maroko, P. R. (1978). Experimental myocardial infarction in the rat: Qualitative and quantitative changes during pathologic evolution. American Journal of Pathology, 90, 57–70.PubMedGoogle Scholar
  18. 18.
    Frangogiannis, N. G., Perrard, J. L., Mendoza, L. H., Burns, A. R., Lindsey, M. L., Ballantyne, C. M., et al. (1998). Stem cell factor induction is associated with mast cell accumulation after canine myocardial ischemia and reperfusion. Circulation, 98, 687–698.PubMedGoogle Scholar
  19. 19.
    Frangogiannis, N. G., Smith, C. W., & Entman, M. L. (2002). The inflammatory response in myocardial infarction. Cardiovascular Research, 53, 31–47.CrossRefPubMedGoogle Scholar
  20. 20.
    Fukushima, S., Coppen, S. R., Lee, J., Yamahara, K., Felkin, L. E., Terracciano, C. M., et al. (2008). Choice of cell-delivery route for skeletal myoblast transplantation for treating post-infarction chronic heart failure in rat. PLoS ONE, 3, e3071.CrossRefPubMedGoogle Scholar
  21. 21.
    Fyhrquist, F. & Saijonmaa, O. (2008). Renin–angiotensin system revisited. Journal of Internal Medicine, 264, 224–236.CrossRefPubMedGoogle Scholar
  22. 22.
    Gavira, J. J., Herreros, J., Perez, A., Garcia-Velloso, M. J., Barba, J., Martin-Herrero, F., et al. (2006). Autologous skeletal myoblast transplantation in patients with nonacute myocardial infarction: 1-year follow-up. Journal of Thoracic and Cardiovascular Surgery, 131, 799–804.CrossRefPubMedGoogle Scholar
  23. 23.
    Gavira, J. J., Nasarre, E., Abizanda, G., Perez-Ilzarbe, M., de Martino-Rodriguez, A., Garcia de Jalon, J. A. et al. (2009). Repeated implantation of skeletal myoblast in a swine model of chronic myocardial infarction. European Heart Journal (in press).Google Scholar
  24. 24.
    Gavira, J. J., Perez-Ilzarbe, M., Abizanda, G., Garcia-Rodriguez, A., Orbe, J., Paramo, J. A., et al. (2006). A comparison between percutaneous and surgical transplantation of autologous skeletal myoblasts in a swine model of chronic myocardial infarction. Cardiovascular Research, 71, 744–753.CrossRefPubMedGoogle Scholar
  25. 25.
    Hamad, E., Mather, P. J., Srinivasan, S., Rubin, S., Whellan, D. J., & Feldman, A. M. (2007). Pharmacologic therapy of chronic heart failure. American Journal of Cardiovascular Drugs, 7, 235–248.CrossRefPubMedGoogle Scholar
  26. 26.
    He, Q., Trindade, P. T., Stumm, M., Li, J., Zammaretti, P., Bettiol, E., et al. (2009). Fate of undifferentiated mouse embryonic stem cells within the rat heart: Role of myocardial infarction and immune suppression. Journal of Cellular and Molecular Medicine, 13, 188–201.CrossRefPubMedGoogle Scholar
  27. 27.
    Holmes, J. W., Borg, T. K., & Covell, J. W. (2005). Structure and mechanics of healing myocardial infarcts. Annual Review of Biomedical Engineering, 7, 223–253.CrossRefPubMedGoogle Scholar
  28. 28.
    Irwin, M. W., Mak, S., Mann, D. L., Qu, R., Penninger, J. M., Yan, A., et al. (1999). Tissue expression and immunolocalization of tumor necrosis factor-alpha in postinfarction dysfunctional myocardium. Circulation, 99, 1492–1498.PubMedGoogle Scholar
  29. 29.
    Kastrup, J., Ripa, R. S., Wang, Y., & Jorgensen, E. (2006). Myocardial regeneration induced by granulocyte-colony-stimulating factor mobilization of stem cells in patients with acute or chronic ischaemic heart disease: A non-invasive alternative for clinical stem cell therapy? European Heart Journal, 27, 2748–2754.CrossRefPubMedGoogle Scholar
  30. 30.
    Kinnaird, T., Stabile, E., Burnett, M. S., Lee, C. W., Barr, S., Fuchs, S., et al. (2004). Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circulation Research, 94, 678–685.CrossRefPubMedGoogle Scholar
  31. 31.
    Koh, G. Y., Klug, M. G., Soonpaa, M. H., & Field, L. J. (1993). Differentiation and long-term survival of C2C12 myoblast grafts in heart. Journal of Clinical Investigation, 92, 1548–1554.CrossRefPubMedGoogle Scholar
  32. 32.
    Laflamme, M. A., Chen, K. Y., Naumova, A. V., Muskheli, V., Fugate, J. A., Dupras, S. K., et al. (2007). Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nature Biotechnology, 25, 1015–1024.CrossRefPubMedGoogle Scholar
  33. 33.
    Landa, N., Miller, L., Feinberg, M. S., Holbova, R., Shachar, M., Freeman, I., et al. (2008). Effect of injectable alginate implant on cardiac remodeling and function after recent and old infarcts in rat. Circulation, 117, 1388–1396.CrossRefPubMedGoogle Scholar
  34. 34.
    Le Blanc, K. (2006). Mesenchymal stromal cells: Tissue repair and immune modulation. Cytotherapy, 8, 559–561.CrossRefPubMedGoogle Scholar
  35. 35.
    Leobon, B., Roncalli, J., Joffre, C., Mazo, M., Boisson, M., Barreau, C., et al. (2009). Adipose-derived cardiomyogenic cells: In vitro expansion and functional improvement in a mouse model of myocardial infarction. Cardiovascular Research, 83, 757–767.CrossRefPubMedGoogle Scholar
  36. 36.
    Li, L., Zhang, S., Zhang, Y., Yu, B., Xu, Y., & Guan, Z. (2008). Paracrine action mediate the antifibrotic effect of transplanted mesenchymal stem cells in a rat model of global heart failure. Molecular Biology Reports, 36, 725–731.CrossRefPubMedGoogle Scholar
  37. 37.
    Li, R. K., Mickle, D. A., Weisel, R. D., Rao, V., & Jia, Z. Q. (2001). Optimal time for cardiomyocyte transplantation to maximize myocardial function after left ventricular injury. Annals of Thoracic Surgery, 72, 1957–1963.CrossRefPubMedGoogle Scholar
  38. 38.
    Li, S. H., Lai, T. Y., Sun, Z., Han, M., Moriyama, E., Wilson, B., et al. (2009). Tracking cardiac engraftment and distribution of implanted bone marrow cells: Comparing intra-aortic, intravenous, and intramyocardial delivery. Journal of Thoracic and Cardiovascular Surgery, 137, 1225–1233. e1221.CrossRefPubMedGoogle Scholar
  39. 39.
    Liu, J. F., Wang, B. W., Hung, H. F., Chang, H., & Shyu, K. G. (2008). Human mesenchymal stem cells improve myocardial performance in a splenectomized rat model of chronic myocardial infarction. Journal of the Formosan Medical Association, 107, 165–174.CrossRefPubMedGoogle Scholar
  40. 40.
    Mann, D. L. (1999). Mechanisms and models in heart failure: A combinatorial approach. Circulation, 100, 999–1008.PubMedGoogle Scholar
  41. 41.
    Mann, D. L., Deswal, A., Bozkurt, B., & Torre-Amione, G. (2002). New therapeutics for chronic heart failure. Annual Review of Medicine, 53, 59–74.CrossRefPubMedGoogle Scholar
  42. 42.
    Martinez-Fernandez, A., Nelson, T. J., Yamada, S., Reyes, S., Alekseev, A. E., Perez-Terzic, C., et al. (2009). iPS programmed without c-MYC yield proficient cardiogenesis for functional heart chimerism. Circulation Research, 105, 648–656.CrossRefPubMedGoogle Scholar
  43. 43.
    Mauritz, C., Schwanke, K., Reppel, M., Neef, S., Katsirntaki, K., Maier, L. S., et al. (2008). Generation of functional murine cardiac myocytes from induced pluripotent stem cells. Circulation, 118, 507–517.CrossRefPubMedGoogle Scholar
  44. 44.
    Mazo, M. (2009). Transplantation of mesenchymal stem cells exerts a greater long-term effect than bone marrow mononuclear cells in a chronic myocardial infarction model in rat. Cell Transplant. doi:10.3727/096368909X480323.
  45. 45.
    Mazo, M., Planat-Benard, V., Abizanda, G., Pelacho, B., Leobon, B., Gavira, J. J., et al. (2008). Transplantation of adipose derived stromal cells is associated with functional improvement in a rat model of chronic myocardial infarction. European Journal of Heart Failure, 10, 454–462.CrossRefPubMedGoogle Scholar
  46. 46.
    Menasche, P. (2009). Stem cell therapy for heart failure: Are arrhythmias a real safety concern? Circulation, 119, 2735–2740.CrossRefPubMedGoogle Scholar
  47. 47.
    Menasche, P., Alfieri, O., Janssens, S., McKenna, W., Reichenspurner, H., Trinquart, L., et al. (2008). The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial: First randomized placebo-controlled study of myoblast transplantation. Circulation, 117, 1189–1200.CrossRefPubMedGoogle Scholar
  48. 48.
    Merx, M. W., Zernecke, A., Liehn, E. A., Schuh, A., Skobel, E., Butzbach, B., et al. (2005). Transplantation of human umbilical vein endothelial cells improves left ventricular function in a rat model of myocardial infarction. Basic Research in Cardiology, 100, 208–216.CrossRefPubMedGoogle Scholar
  49. 49.
    Mias, C., Lairez, O., Trouche, E., Roncalli, J., Calise, D., Seguelas, M. H. et al. (2009). Mesenchymal stem cells promote matrix metalloproteinase secretion by cardiac fibroblasts and reduce cardiac ventricular fibrosis after myocardial infarction. Stem Cells, 27(11), 2734–2743.Google Scholar
  50. 50.
    Miranville, A., Heeschen, C., Sengenes, C., Curat, C. A., Busse, R., & Bouloumie, A. (2004). Improvement of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation, 110, 349–355.CrossRefPubMedGoogle Scholar
  51. 51.
    Miyahara, Y., Nagaya, N., Kataoka, M., Yanagawa, B., Tanaka, K., Hao, H., et al. (2006). Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nature Medicine, 12, 459–465.CrossRefPubMedGoogle Scholar
  52. 52.
    Nahrendorf, M., Swirski, F. K., Aikawa, E., Stangenberg, L., Wurdinger, T., Figueiredo, J. L., et al. (2007). The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. Journal of Experimental Medicine, 204, 3037–3047.CrossRefPubMedGoogle Scholar
  53. 53.
    Nakajima, H., Sakakibara, Y., Tambara, K., Marui, A., Yoshimoto, M., Premaratne, G. U., et al. (2008). Delivery route in bone marrow cell transplantation should be optimized according to the etiology of heart disease. Circ J, 72, 1528–1535.CrossRefPubMedGoogle Scholar
  54. 54.
    Nelson, T. J., Martinez-Fernandez, A., Yamada, S., Perez-Terzic, C., Ikeda, Y., Terzic, A. (2009) Repair of acute myocardial infarction with induced pluripotent stem cells induced by human stemness factors. Circulation. doi:10.1161/CIRCULATIONAHA.109.865154.
  55. 55.
    Nian, M., Lee, P., Khaper, N., & Liu, P. (2004). Inflammatory cytokines and postmyocardial infarction remodeling. Circulation Research, 94, 1543–1553.CrossRefPubMedGoogle Scholar
  56. 56.
    Nussbaum, J., Minami, E., Laflamme, M. A., Virag, J. A., Ware, C. B., Masino, A., et al. (2007). Transplantation of undifferentiated murine embryonic stem cells in the heart: Teratoma formation and immune response. FASEB Journal, 21, 1345–1357.CrossRefPubMedGoogle Scholar
  57. 57.
    Organization WH (2004) The world health report 2004.Google Scholar
  58. 58.
    Orlic, D., Kajstura, J., Chimenti, S., Bodine, D. M., Leri, A., & Anversa, P. (2001). Transplanted adult bone marrow cells repair myocardial infarcts in mice. Annals of the New York Academy of Sciences, 938, 221–229. discussion 229–230.PubMedCrossRefGoogle Scholar
  59. 59.
    Orlic, D., Kajstura, J., Chimenti, S., Jakoniuk, I., Anderson, S. M., Li, B., et al. (2001). Bone marrow cells regenerate infarcted myocardium. Nature, 410, 701–705.CrossRefPubMedGoogle Scholar
  60. 60.
    Ott, H. C., Matthiesen, T. S., Goh, S. K., Black, L. D., Kren, S. M., Netoff, T. I., et al. (2008). Perfusion-decellularized matrix: Using nature’s platform to engineer a bioartificial heart. Nature Medicine, 14, 213–221.CrossRefPubMedGoogle Scholar
  61. 61.
    Pearl, J. & Wu, J. C. (2008). Seeing is believing: Tracking cells to determine the effects of cell transplantation. Seminars in Thoracic and Cardiovascular Surgery, 20, 102–109.CrossRefPubMedGoogle Scholar
  62. 62.
    Pelacho, B. & Prosper, F. (2008). Stem cells and cardiac disease: Where are we going? Curr Stem Cell Res Ther, 3, 265–276.CrossRefPubMedGoogle Scholar
  63. 63.
    Perez-Ilzarbe, M., Agbulut, O., Pelacho, B., Ciorba, C., San, Jose-Eneriz E., Desnos, M., et al. (2008). Characterization of the paracrine effects of human skeletal myoblasts transplanted in infarcted myocardium. European Journal of Heart Failure, 10, 1065–1072.CrossRefPubMedGoogle Scholar
  64. 64.
    Pfannkuche, K., Liang, H., Hannes, T., Xi, J., Fatima, A., Nguemo, F., et al. (2009). Cardiac myocytes derived from murine reprogrammed fibroblasts: Intact hormonal regulation, cardiac ion channel expression and development of contractility. Cellular Physiology and Biochemistry, 24, 73–86.CrossRefPubMedGoogle Scholar
  65. 65.
    Phillips, H. R., O’Connor, C. M., & Rogers, J. (2007). Revascularization for heart failure. American Heart Journal, 153, 65–73.CrossRefPubMedGoogle Scholar
  66. 66.
    Planat-Benard, V., Menard, C., Andre, M., Puceat, M., Perez, A., Garcia-Verdugo, J. M., et al. (2004). Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells. Circulation Research, 94, 223–229.CrossRefPubMedGoogle Scholar
  67. 67.
    Puymirat, E., Geha, R., Tomescot, A., Bellamy, V., Larghero, J., Trinquart, L., et al. (2009). Can mesenchymal stem cells induce tolerance to cotransplanted human embryonic stem cells? Molecular Therapy, 17, 176–182.CrossRefPubMedGoogle Scholar
  68. 68.
    Richard, V., Murry, C. E., & Reimer, K. A. (1995). Healing of myocardial infarcts in dogs. Effects of late reperfusion. Circulation, 92, 1891–1901.PubMedGoogle Scholar
  69. 69.
    Roger, V. L., Weston, S. A., Redfield, M. M., Hellermann-Homan, J. P., Killian, J., Yawn, B. P., et al. (2004). Trends in heart failure incidence and survival in a community-based population. Jama, 292, 344–350.CrossRefPubMedGoogle Scholar
  70. 70.
    Rossen, R. D., Michael, L. H., Kagiyama, A., Savage, H. E., Hanson, G., Reisberg, M. A., et al. (1988). Mechanism of complement activation after coronary artery occlusion: Evidence that myocardial ischemia in dogs causes release of constituents of myocardial subcellular origin that complex with human C1q in vivo. Circulation Research, 62, 572–584.PubMedGoogle Scholar
  71. 71.
    Rota, M., Kajstura, J., Hosoda, T., Bearzi, C., Vitale, S., Esposito, G., 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, 17783–17788.CrossRefPubMedGoogle Scholar
  72. 72.
    Schaffler, A. & Buchler, C. (2007). Concise review: Adipose tissue-derived stromal cells—Basic and clinical implications for novel cell-based therapies. Stem Cells, 25, 818–827.CrossRefPubMedGoogle Scholar
  73. 73.
    Schuleri, K. H., Feigenbaum, G. S., Centola, M., Weiss, E. S., Zimmet, J. M., Turney, J., et al. (2009). Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy. European Heart Journal, 30, 2722–2732.CrossRefPubMedGoogle Scholar
  74. 74.
    Segers, V. F. & Lee, R. T. (2008). Stem-cell therapy for cardiac disease. Nature, 451, 937–942.CrossRefPubMedGoogle Scholar
  75. 75.
    Shanmugam, G. & Legare, J. F. (2008). Revascularization for ischaemic cardiomyopathy. Current Opinion in Cardiology, 23, 148–152.CrossRefPubMedGoogle Scholar
  76. 76.
    Shintani, Y., Fukushima, S., Varela-Carver, A., Lee, J., Coppen, S. R., Takahashi, K., et al. (2009). Donor cell type-specific paracrine effects of cell transplantation for post-infarction heart failure. Journal of Molecular and Cellular Cardiology, 47, 288–295.CrossRefPubMedGoogle Scholar
  77. 77.
    Silva, G. V., Litovsky, S., Assad, J. A., Sousa, A. L., Martin, B. J., Vela, D., et al. (2005). Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation, 111, 150–156.CrossRefPubMedGoogle Scholar
  78. 78.
    Strem, B. M., Hicok, K. C., Zhu, M., Wulur, I., Alfonso, Z., Schreiber, R. E., et al. (2005). Multipotential differentiation of adipose tissue-derived stem cells. Keio Journal of Medicine, 54, 132–141.CrossRefPubMedGoogle Scholar
  79. 79.
    Sun, Y., Kiani, M. F., Postlethwaite, A. E., & Weber, K. T. (2002). Infarct scar as living tissue. Basic Research in Cardiology, 97, 343–347.CrossRefPubMedGoogle Scholar
  80. 80.
    Takahashi, K. & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126, 663–676.CrossRefPubMedGoogle Scholar
  81. 81.
    Takehara, N., Tsutsumi, Y., Tateishi, K., Ogata, T., Tanaka, H., Ueyama, T., et al. (2008). Controlled delivery of basic fibroblast growth factor promotes human cardiosphere-derived cell engraftment to enhance cardiac repair for chronic myocardial infarction. J Am Coll Cardiol, 52, 1858–1865.CrossRefPubMedGoogle Scholar
  82. 82.
    Taylor, D. A., Atkins, B. Z., Hungspreugs, P., Jones, T. R., Reedy, M. C., Hutcheson, K. A., et al. (1998). Regenerating functional myocardium: Improved performance after skeletal myoblast transplantation. Nature Medicine, 4, 929–933.CrossRefPubMedGoogle Scholar
  83. 83.
    van Amerongen, M. J., Bou-Gharios, G., Popa, E., van Ark, J., Petersen, A. H., van Dam, G. M., et al. (2008). Bone marrow-derived myofibroblasts contribute functionally to scar formation after myocardial infarction. J Pathol, 214, 377–386.CrossRefPubMedGoogle Scholar
  84. 84.
    Vandervelde, S., van Amerongen, M. J., Tio, R. A., Petersen, A. H., van Luyn, M. J., & Harmsen, M. C. (2006). Increased inflammatory response and neovascularization in reperfused vs. non-reperfused murine myocardial infarction. Cardiovasc Pathol, 15, 83–90.CrossRefPubMedGoogle Scholar
  85. 85.
    Virag, J. I. & Murry, C. E. (2003). Myofibroblast and endothelial cell proliferation during murine myocardial infarct repair. American Journal of Pathology, 163, 2433–2440.PubMedGoogle Scholar
  86. 86.
    Waksman, R., Fournadjiev, J., Baffour, R., Pakala, R., Hellinga, D., Leborgne, L., et al. (2004). Transepicardial autologous bone marrow-derived mononuclear cell therapy in a porcine model of chronically infarcted myocardium. Cardiovasc Radiat Med, 5, 125–131.CrossRefPubMedGoogle Scholar
  87. 87.
    Weisman, H. F., Bush, D. E., Mannisi, J. A., Weisfeldt, M. L., & Healy, B. (1988). Cellular mechanisms of myocardial infarct expansion. Circulation, 78, 186–201.PubMedGoogle Scholar
  88. 88.
    Yu, J., Christman, K. L., Chin, E., Sievers, R. E., Saeed, M., & Lee, R. J. (2009). Restoration of left ventricular geometry and improvement of left ventricular function in a rodent model of chronic ischemic cardiomyopathy. Journal of Thoracic and Cardiovascular Surgery, 137, 180–187.CrossRefPubMedGoogle Scholar
  89. 89.
    Yu, J., Gu, Y., Du, K. T., Mihardja, S., Sievers, R. E., & Lee, R. J. (2008). The effect of injected RGD modified alginate on angiogenesis and left ventricular function in a chronic rat infarct model. Biomaterials, 30, 751–756.CrossRefPubMedGoogle Scholar
  90. 90.
    Zhang, J., Wilson, G. F., Soerens, A. G., Koonce, C. H., Yu, J., Palecek, S. P., et al. (2009). Functional cardiomyocytes derived from human induced pluripotent stem cells. Circulation Research, 104, e30–41.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Hematology and Cell Therapy, Clinica Universidad de Navarra, and Division of Cancer, Foundation for Applied Medical ResearchUniversity of NavarraPamplonaSpain

Personalised recommendations