Optimizing Cardiac Repair and Regeneration Through Activation of the Endogenous Cardiac Stem Cell Compartment

  • Georgina M. Ellison
  • Bernardo Nadal-Ginard
  • Daniele Torella


Given the aging of the Western World and declining death rates due to acute coronary syndromes, the increasing trends in the magnitude and morbidity of heart failure (HF) are predicted to continue for the foreseeable future. It is imperative to develop effective therapies for the amelioration and prevention of HF. The search for the best cell type to be used in clinical protocols of cardiac regeneration is still on. That the adult mammalian heart harbors endogenous, multipotent cardiac stem/progenitor cells (eCSCs) and that cardiomyocytes are replaced throughout adulthood represent a paradigm shift in cardiovascular biology. The presence of eCSCs supports the view that the heart can repair itself if the eCSCs can be properly stimulated. Pending a better understanding of eCSC biology, it should be possible to replace autologous cell transplantation-based myocardial regeneration protocols with an “off-the-shelf,” readily available, and effective regenerative/reparative therapy based on activation of the eCSCs in situ.


Endogenous cardiac stem/progenitor cells Growth factors Paracrine Allogeneic Myocardial regeneration Multipotent 


  1. 1.
    Kahan, B. D. (2011). Fifty years in the vineyard of transplantation: Looking back. Transplantation Proceedings, 43, 2853–2859.PubMedCrossRefGoogle Scholar
  2. 2.
    Roger, V. L., Go, A. S., Lloyd-Jones, D. M., et al. (2012). American heart association statistics committee and stroke statistics subcommittee. Heart disease and stroke statistics—2012 update: A report from the american heart association. Circulation, 125, 2–220.CrossRefGoogle Scholar
  3. 3.
    Jessup, M., & Brozena, S. (2003). Heart failure. The New England Journal of Medicine, 348, 2007–2018.PubMedCrossRefGoogle Scholar
  4. 4.
    Terzic, A., & Nelson, T. J. (2010). Regenerative medicine advancing health care 2020. Journal of the American College of Cardiology, 55, 2254–2257.PubMedCrossRefGoogle Scholar
  5. 5.
    Mercier, F. E., Ragu, C., & Scadden, D. T. (2011). The bone marrow at the crossroads of blood and immunity. Nature Reviews Immunology, 12, 49–60.PubMedCrossRefGoogle Scholar
  6. 6.
    Simons, B. D., & Clevers, H. (2011). Stem cell self-renewal in intestinal crypt. Experimental Cell Research, 317, 2719–2724.PubMedCrossRefGoogle Scholar
  7. 7.
    Fuchs, E. (2009). The tortoise and the hair: slow-cycling cells in the stem cell race. Cell, 137, 811–819.PubMedCrossRefGoogle Scholar
  8. 8.
    Badylak, S. F., Weiss, D. J., Caplan, A., & Macchiarini, P. (2012). Engineered whole organs and complex tissues. Lancet, 379, 943–952.PubMedCrossRefGoogle Scholar
  9. 9.
    Evans, M. J., & Kaufman, M. H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature, 292, 154–156.PubMedCrossRefGoogle Scholar
  10. 10.
    Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282, 1145–1147.PubMedCrossRefGoogle Scholar
  11. 11.
    Murry, C. E., & Keller, G. (2008). Differentiation of embryonic stem cells to clinically relevant populations: Lessons from embryonic development. Cell, 132, 661–680.PubMedCrossRefGoogle Scholar
  12. 12.
    Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126, 663–676.PubMedCrossRefGoogle Scholar
  13. 13.
    Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., et al. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131, 861–872.PubMedCrossRefGoogle Scholar
  14. 14.
    Yamanaka, S. (2007). Strategies and new developments in the generation of patient-specific pluripotent stem cells. Cell Stem Cell, 1, 39–49.PubMedCrossRefGoogle Scholar
  15. 15.
    Robinton, D. A., & Daley, G. Q. (2012). The promise of induced pluripotent stem cells in research and therapy. Nature, 481, 295–305.PubMedCrossRefGoogle Scholar
  16. 16.
    Rountree, C. B., Mishra, L., & Willenbring, H. (2012). Stem cells in liver diseases and cancer: recent advances on the path to new therapies. Hepatology, 55, 298–306.PubMedCrossRefGoogle Scholar
  17. 17.
    Reule, S., & Gupta, S. (2011). Kidney regeneration and resident stem cells. Organogenesis, 7, 135–139.PubMedCrossRefGoogle Scholar
  18. 18.
    Kopp, J. L., Dubois, C. L., Hao, E., Thorel, F., Herrera, P. L., & Sander, M. (2011). Progenitor cell domains in the developing and adult pancreas. Cell Cycle, 10, 1921–1927.PubMedCrossRefGoogle Scholar
  19. 19.
    Kotton, D. N. (2012). Next generation regeneration: the hope and hype of lung stem cell research. American Journal of Respiratory and Critical Care Medicine. doi:10.1164/rccm.201202-0228PP.
  20. 20.
    Buckingham, M., & Montarras, D. (2008). Skeletal muscle stem cells. Current Opinion in Genetics and Development, 18, 330–336.PubMedCrossRefGoogle Scholar
  21. 21.
    Suh, H., Deng, W., & Gage, F. H. (2009). Signaling in adult neurogenesis. Annual Review of Cell and Developmental Biology, 25, 253–275.PubMedCrossRefGoogle Scholar
  22. 22.
    Hunter, J. J., & Chien, K. R. (1999). Signaling pathways for cardiac hypertrophy and failure. The New England Journal of Medicine, 341, 1276–1283.PubMedCrossRefGoogle Scholar
  23. 23.
    Soonpaa, M. H., & Field, L. J. (1998). Survey of studies examining mammalian cardiomyocyte DNA synthesis. Circulation Research, 83, 15–26.PubMedCrossRefGoogle Scholar
  24. 24.
    Laflamme, M. A., & Murry, C. E. (2011). Heart regeneration. Nature, 473, 326–335.PubMedCrossRefGoogle Scholar
  25. 25.
    Nadal-Ginard, B. (1978). Commitment, fusion and biochemical differentiation of a myogenic cell line in the absence of DNA synthesis. Cell, 15, 855–864.PubMedCrossRefGoogle Scholar
  26. 26.
    Chien, K. R., & Olson, E. N. (2002). Converging pathways and principles in heart development and disease: CV@CSH. Cell, 110, 153–162.PubMedCrossRefGoogle Scholar
  27. 27.
    Oh, H., Taffet, G. E., Youker, K. A., Entman, M. L., Overbeek, P. A., Michael, L. H., et al. (2001). Telomerase reverse transcriptase promotes cardiac muscle cell proliferation, hypertrophy, and survival. Proceedings of the National Academy of Sciences of the United States of America, 98, 10308–10313.PubMedCrossRefGoogle Scholar
  28. 28.
    Beltrami, A. P., Urbanek, K., Kajstura, J., Yan, S. M., Finato, N., Bussani, R., et al. (2001). Evidence that human cardiac myocytes divide after myocardial infarction. The New England Journal of Medicine, 344, 1750–1757.PubMedCrossRefGoogle Scholar
  29. 29.
    Quaini, F., Urbanek, K., Beltrami, A. P., Finato, N., Beltrami, C. A., Nadal-Ginard, B., et al. (2002). Chimerism of the transplanted heart. The New England Journal of Medicine, 346, 5–15.PubMedCrossRefGoogle Scholar
  30. 30.
    Urbanek, K., Quaini, F., Tasca, G., Torella, D., Castaldo, C., Nadal-Ginard, B., et al. (2003). Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy. Proceedings of the National Academy of Sciences of the United States of America, 100, 10440–10445.PubMedCrossRefGoogle Scholar
  31. 31.
    Urbanek, K., Torella, D., Sheikh, F., De Angelis, A., Nurzynska, D., Silvestri, F., et al. (2005). Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proceedings of the National Academy of Sciences of the United States of America, 102, 8692–8697.PubMedCrossRefGoogle Scholar
  32. 32.
    Anversa, P., & Nadal-Ginard, B. (2002). Myocyte renewal and ventricular remodelling. Nature, 415, 240–243.PubMedCrossRefGoogle Scholar
  33. 33.
    Nadal-Ginard, B., Kajstura, J., Leri, A., & Anversa, P. (2003). Myocyte death, growth, and regeneration in cardiac hypertrophy and failure. Circulation Research, 92, 139–150.PubMedCrossRefGoogle Scholar
  34. 34.
    Bergmann, O., Bhardwaj, R. D., Bernard, S., Zdunek, S., Barnabé-Heider, F., Walsh, S., et al. (2009). Evidence for cardiomyocyte renewal in humans. Science, 324, 98–102.PubMedCrossRefGoogle Scholar
  35. 35.
    Hsieh, P. C., Segers, V. F., Davis, M. E., MacGillivray, C., Gannon, J., Molkentin, J. D., et al. (2007). Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury. Nature Medicine, 13, 970–974.PubMedCrossRefGoogle Scholar
  36. 36.
    Boström, P., Mann, N., Wu, J., Quintero, P. A., Plovie, E. R., Panáková, D., et al. (2010). C/EBPβ controls exercise-induced cardiac growth and protects against pathological cardiac remodeling. Cell, 143, 1072–1083.PubMedCrossRefGoogle Scholar
  37. 37.
    Kajstura, J., Gurusamy, N., Ogórek, B., Goichberg, P., Clavo-Rondon, C., Hosoda, T., et al. (2010). Myocyte turnover in the aging human heart. Circulation Research, 107, 1374–1386.PubMedCrossRefGoogle Scholar
  38. 38.
    Bersell, K., Arab, S., Haring, B., & Kühn, B. (2009). Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury. Cell, 138, 257–270.PubMedCrossRefGoogle Scholar
  39. 39.
    Kühn, B., del Monte, F., Hajjar, R. J., Chang, Y. S., Lebeche, D., Arab, S., et al. (2007). Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair. Nature Medicine, 13, 962–969.PubMedCrossRefGoogle Scholar
  40. 40.
    Torella, D., Ellison, G. M., Karakikes, I., & Nadal-Ginard, B. (2007). Resident cardiac stem cells. Cellular and Molecular Life Sciences, 64, 661–673.PubMedCrossRefGoogle Scholar
  41. 41.
    Rasmussen, T. L., Raveendran, G., Zhang, J., & Garry, D. J. (2011). Getting to the heart of myocardial stem cells and cell therapy. Circulation, 123, 1771–1779.PubMedCrossRefGoogle Scholar
  42. 42.
    Eisenberg, C. A., Burch, J. B., & Eisenberg, L. M. (2006). Bone marrow cells transdifferentiate to cardiomyocytes when introduced into the embryonic heart. Stem Cells, 24, 1236–1245.PubMedCrossRefGoogle Scholar
  43. 43.
    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.PubMedCrossRefGoogle Scholar
  44. 44.
    Loffredo, F. S., Steinhauser, M. L., Gannon, J., & Lee, R. T. (2011). Bone marrow-derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair. Cell Stem Cell, 8, 389–398.PubMedCrossRefGoogle Scholar
  45. 45.
    Srivastava, D., & Ivey, K. N. (2006). Potential of stem-cell-based therapies for heart disease. Nature, 441, 1097–1099.PubMedCrossRefGoogle Scholar
  46. 46.
    Beltrami, A. P., Barlucchi, L., Torella, D., Baker, M., Limana, F., Chimenti, S., et al. (2003). Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell, 114, 763–776.PubMedCrossRefGoogle Scholar
  47. 47.
    Oh, H., Bradfute, S. B., Gallardo, T. D., Nakamura, T., Gaussin, V., Mishina, Y., et al. (2003). Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proceedings of the National Academy of Sciences of the United States of America, 100, 12313–12318.PubMedCrossRefGoogle Scholar
  48. 48.
    Matsuura, K., Nagai, T., Nishigaki, N., Oyama, T., Nishi, J., Wada, H., et al. (2004). Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. The Journal of Biological Chemistry, 279, 11384–11391.PubMedCrossRefGoogle Scholar
  49. 49.
    Messina, E., De Angelis, L., Frati, G., Morrone, S., Chimenti, S., Fiordaliso, F., et al. (2004). Isolation and expansion of adult cardiac stem cells from human and murine heart. Circulation Research, 95, 911–921.PubMedCrossRefGoogle Scholar
  50. 50.
    Martin, C. M., Meeson, A. P., Robertson, S. M., Hawke, T. J., Richardson, J. A., Bates, S., et al. (2004). Persistent expression of the ATP-binding cassette transporter, Abcg2, identifies cardiac SP cells in the developing and adult heart. Developments in Biologicals, 265, 262–275.CrossRefGoogle Scholar
  51. 51.
    Laugwitz, K. L., Moretti, A., Lam, J., Gruber, P., Chen, Y., Woodard, S., et al. (2005). Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature, 433, 647–653.PubMedCrossRefGoogle Scholar
  52. 52.
    Moretti, A., Caron, L., Nakano, A., Lam, J. T., Bernshausen, A., Chen, Y., et al. (2006). Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell, 127, 1151–1165.PubMedCrossRefGoogle Scholar
  53. 53.
    Kattman, S. J., Huber, T. L., & Keller, G. M. (2006). Multipotent flk-1+ cardiovascular progenitor cells give rise to the cardiomyocyte, endothelial, and vascular smooth muscle lineages. Developmental Cell, 11, 723–732.PubMedCrossRefGoogle Scholar
  54. 54.
    Wu, S. M., Fujiwara, Y., Cibulsky, S. M., Clapham, D. E., Lien, C. L., Schultheiss, T. M., et al. (2006). Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart. Cell, 127, 1137–1150.PubMedCrossRefGoogle Scholar
  55. 55.
    Smart, N., Bollini, S., Dubé, K. N., Vieira, J. M., Zhou, B., Davidson, S., et al. (2011). De novo cardiomyocytes from within the activated adult heart after injury. Nature, 474, 640–644.PubMedCrossRefGoogle Scholar
  56. 56.
    Ellison, G. M., Galuppo, V., Vicinanza, C., Aquila, I., Waring, C. D., Leone, A., et al. (2010). Cardiac stem and progenitor cell identification: different markers for the same cell? Frontiers in Bioscience, 2, 641–652.CrossRefGoogle Scholar
  57. 57.
    Chong, J. J., Chandrakanthan, V., Xaymardan, M., Asli, N. S., Li, J., Ahmed, I., et al. (2011). Adult cardiac-resident MSC-like stem cells with a proepicardial origin. Cell Stem Cell, 9, 527–540.PubMedCrossRefGoogle Scholar
  58. 58.
    Ellison, G. M., Torella, D., Karakikes, I., & Nadal-Ginard, B. (2007). Myocyte death and renewal: modern concepts of cardiac cellular homeostasis. Nature Clinical Practice. Cardiovascular Medicine, 4(Suppl 1), S52–S59.PubMedCrossRefGoogle Scholar
  59. 59.
    Ellison, G. M., Waring, C. D., Vicinanza, C., & Torella, D. (2012). Physiological cardiac remodelling in response to endurance exercise training: cellular and molecular mechanisms. Heart, 98, 5–10.PubMedCrossRefGoogle Scholar
  60. 60.
    Ellison, G. M., Torella, D., Karakikes, I., Purushothaman, S., Curcio, A., Gasparri, C., et al. (2007). Acute beta-adrenergic overload produces myocyte damage through calcium leakage from the ryanodine receptor 2 but spares cardiac stem cells. The Journal of Biological Chemistry, 282, 11397–11409.PubMedCrossRefGoogle Scholar
  61. 61.
    Nadal-Ginard, B., & Fuster, V. (2007). Myocardial cell therapy at the crossroads. Nature Clinical Practice. Cardiovascular Medicine, 4, 1.PubMedCrossRefGoogle Scholar
  62. 62.
    Janssens, S. (2010). Stem cells in the treatment of heart disease. Annual Review of Medicine, 61, 287–300.PubMedCrossRefGoogle Scholar
  63. 63.
    Abdel-Latif, A., Bolli, R., Tleyjeh, I. M., Montori, V. M., Perin, E. C., Hornung, C. A., et al. (2007). Adult bone marrow-derived cells for cardiac repair: A systematic review and meta-analysis. Archives of Internal Medicine, 167, 989–997.PubMedCrossRefGoogle Scholar
  64. 64.
    Murry, C. E., Field, L. J., & Menasché, P. (2005). Cell-based cardiac repair: Reflections at the 10-year point. Circulation, 112, 3174–3183.PubMedCrossRefGoogle Scholar
  65. 65.
    Janssens, S. P. (2011). Cardiac bone marrow cell therapy: The proof of the pudding remains in the eating. European Heart Journal, 32, 1697–1700.PubMedCrossRefGoogle Scholar
  66. 66.
    Gnecchi, M., Zhang, Z., Ni, A., & Dzau, V. J. (2008). Paracrine mechanisms in adult stem cell signaling and therapy. Circulation Research, 103, 1204–1219.PubMedCrossRefGoogle Scholar
  67. 67.
    Kubal, C., Sheth, K., Nadal-Ginard, B., & Galiñanes, M. (2006). Bone marrow cells have a potent anti-ischemic effect against myocardial cell death in humans. The Journal of Thoracic and Cardiovascular Surgery, 132, 1112–1118.PubMedCrossRefGoogle Scholar
  68. 68.
    Lai, V. K., Linares-Palomino, J., Nadal-Ginard, B., & Galiñanes, M. (2009). Bone marrow cell-induced protection of the human myocardium: Characterization and mechanism of action. The Journal of Thoracic and Cardiovascular Surgery, 138, 1400–1408.PubMedCrossRefGoogle Scholar
  69. 69.
    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.PubMedCrossRefGoogle Scholar
  70. 70.
    Kinnaird, T., Stabile, E., Burnett, M. S., Shou, M., Lee, C. W., Barr, S., et al. (2004). Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation, 109, 1543–1549.PubMedCrossRefGoogle Scholar
  71. 71.
    Dimmeler, S., Burchfield, J., & Zeiher, A. M. (2008). Cell-based therapy of myocardial infarction. Arteriosclerosis, Thrombosis, and Vascular Biology, 28, 208–216.PubMedCrossRefGoogle Scholar
  72. 72.
    Hatzistergos, K. E., Quevedo, H., Oskouei, B. N., Hu, Q., Feigenbaum, G. S., Margitich, I. S., et al. (2010). Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation. Circulation Research, 107, 913–922.PubMedCrossRefGoogle Scholar
  73. 73.
    Behfar, A., Yamada, S., Crespo-Diaz, R., Nesbitt, J. J., Rowe, L. A., Perez-Terzic, C., et al. (2010). Guided cardiopoiesis enhances therapeutic benefit of bone marrow human mesenchymal stem cells in chronic myocardial infarction. Journal of the American College of Cardiology, 56, 721–734.PubMedCrossRefGoogle Scholar
  74. 74.
    Ellison, G. M., Torella, D., Dellegrottaglie, S., Perez-Martinez, C., Perez de Prado, A., Vicinanza, C., et al. (2011). Endogenous cardiac stem cell activation by insulin-like growth factor-1/hepatocyte growth factor intracoronary injection fosters survival and regeneration of the infarcted pig heart. Journal of the American College of Cardiology, 58, 977–986.PubMedCrossRefGoogle Scholar
  75. 75.
    Bolli, R., Chugh, A. R., D'Amario, D., Loughran, J. H., Stoddard, M. F., Ikram, S., et al. (2011). Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): Initial results of a randomised phase 1 trial. Lancet, 378, 1847–1857.PubMedCrossRefGoogle Scholar
  76. 76.
    Makkar, R. R., Smith, R. R., Cheng, K., Malliaras, K., Thomson, L. E., Berman, D., et al. (2012). Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): A prospective, randomised phase 1 trial. Lancet, 379, 895–904.PubMedCrossRefGoogle Scholar
  77. 77.
    Torella, D., Rota, M., Nurzynska, D., Musso, E., Monsen, A., Shiraishi, I., et al. (2004). Cardiac stem cell and myocyte aging, heart failure, and insulin-like growth factor-1 overexpression. Circulation Research, 94, 514–524.PubMedCrossRefGoogle Scholar
  78. 78.
    Chimenti, C., Kajstura, J., Torella, D., Urbanek, K., Heleniak, H., Colussi, C., et al. (2003). Senescence and death of primitive cells and myocytes lead to premature cardiac aging and heart failure. Circulation Research, 93, 604–613.PubMedCrossRefGoogle Scholar
  79. 79.
    Torella, D., Ellison, G. M., Méndez-Ferrer, S., Ibanez, B., & Nadal-Ginard, B. (2006). Resident human cardiac stem cells: role in cardiac cellular homeostasis and potential for myocardial regeneration. Nature Clinical Practice. Cardiovascular Medicine, 3(Suppl 1), S8–S13.PubMedCrossRefGoogle Scholar
  80. 80.
    Ranganath, S. H., Levy, O., Inamdar, M. S., & Karp, J. M. (2012). Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease. Cell Stem Cell, 10, 244–258.PubMedCrossRefGoogle Scholar
  81. 81.
    Medicetty, S., Wiktor, D., Lehman, N., Raber, A., Popović, Z. B., Deans, R., et al. (2011). Percutaneous adventitial delivery of allogeneic bone marrow derived stem cells via infarct related artery improves long-term ventricular function in acute myocardial infarction. Cell Transplantation. doi:10.3727/096368911X603657.
  82. 82.
    Penn, M. S., Ellis, S., Gandhi, S., Greenbaum, A., Hodes, Z., Mendelsohn, F. O., et al. (2012). Adventitial delivery of an allogeneic bone marrow-derived adherent stem cell in acute myocardial infarction: Phase I clinical study. Circulation Research, 110, 304–311.PubMedCrossRefGoogle Scholar
  83. 83.
    Malliaras, K., Li, T. S., Luthringer, D., Terrovitis, J., Cheng, K., Chakravarty, T., et al. (2012). Safety and efficacy of allogeneic cell therapy in infarcted rats transplanted with mismatched cardiosphere-derived cells. Circulation, 125, 100–112.PubMedCrossRefGoogle Scholar
  84. 84.
    Kawaguchi, N., Smith, A. J., Waring, C. D., Hasan, M. K., Miyamoto, S., Matsuoka, R., et al. (2010). c-kitpos GATA-4 high rat cardiac stem cells foster adult cardiomyocyte survival through IGF-1 paracrine signalling. PLoS One, 5, e14297.PubMedCrossRefGoogle Scholar
  85. 85.
    Hofmann, M., Wollert, K. C., Meyer, G. P., Menke, A., Arseniev, L., Hertenstein, B., et al. (2005). Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation, 111, 2198–2202.PubMedCrossRefGoogle Scholar
  86. 86.
    Ellison, G. M., Torella, D., Trigueros, C., Gonzalez, A., Waring, C., Perez-Martinez, C., et al. (2009). Use of heterologous non-matched cardiac stem cells (CSCs) without immunosuppression as an effective regenerating agent in a porcine model of acute myocardial infarction. European Heart Journal, 30(Abstract Supplement), 495.Google Scholar
  87. 87.
    Quevedo, H. C., Hatzistergos, K. E., Oskouei, B. N., Feigenbaum, G. S., Rodriguez, J. E., Valdes, D., et al. (2009). Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity. Proceedings of the National Academy of Sciences of the United States of America, 106, 14022–14027.PubMedCrossRefGoogle Scholar
  88. 88.
    Huang, X. P., Sun, Z., Miyagi, Y., McDonald Kinkaid, H., Zhang, L., Weisel, R. D., et al. (2010). Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and limits their long-term benefits for myocardial repair. Circulation, 122, 2419–2429.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Georgina M. Ellison
    • 1
    • 2
  • Bernardo Nadal-Ginard
    • 1
  • Daniele Torella
    • 2
    • 1
  1. 1.Stem Cell & Regenerative Biology Unit (BioStem), RISESLiverpool John Moores UniversityLiverpoolUK
  2. 2.Molecular and Cellular Cardiology, Department of Medical and Surgical SciencesMagna Graecia UniversityCatanzaroItaly

Personalised recommendations