Stem Cell Reviews and Reports

, Volume 9, Issue 3, pp 281–302

Optimization of the Cardiovascular Therapeutic Properties of Mesenchymal Stromal/Stem Cells–Taking the Next Step

  • James D. Richardson
  • Adam J. Nelson
  • Andrew C. W. Zannettino
  • Stan Gronthos
  • Stephen G. Worthley
  • Peter J. Psaltis
Article

Abstract

Despite current treatment options, cardiac failure is associated with significant morbidity and mortality highlighting a compelling clinical need for novel therapeutic approaches. Based on promising pre-clinical data, stem cell therapy has been suggested as a possible therapeutic strategy. Of the candidate cell types evaluated, mesenchymal stromal/stem cells (MSCs) have been widely evaluated due to their ease of isolation and ex vivo expansion, potential allogeneic utility and capacity to promote neo-angiogenesis and endogenous cardiac repair. However, the clinical application of MSCs for mainstream cardiovascular use is currently hindered by several important limitations, including suboptimal retention and engraftment and restricted capacity for bona fide cardiomyocyte regeneration. Consequently, this has prompted intense efforts to advance the therapeutic properties of MSCs for cardiovascular disease. In this review, we consider the scope of benefit from traditional plastic adherence-isolated MSCs and the lessons learned from their conventional use in preclinical and clinical studies. Focus is then given to the evolving strategies aimed at optimizing MSC therapy, including discussion of cell-targeted techniques that encompass the preparation, pre-conditioning and manipulation of these cells ex vivo, methods to improve their delivery to the heart and innovative substrate-directed strategies to support their interaction with the host myocardium.

Keywords

Cardiomyopathy Ischemic heart disease Limitations Mesenchymal stem cells Mesenchymal precursor cells Myocardial infarction Optimization Paracrine Pre-conditioning Tissue engineering 

References

  1. 1.
    Ho, K., Anderson, K., Kannel, W., Grossman, W., & Levy, D. (1993). Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation, 88, 107–115.PubMedGoogle Scholar
  2. 2.
    Fuchs, S., Baffour, R., Zhou, Y. F., et al. (2001). Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia. Journal of the American College of Cardiology, 37, 1726–1732.PubMedGoogle Scholar
  3. 3.
    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, 1199–1209.PubMedGoogle Scholar
  4. 4.
    Orlic, D., Kajstura, J., Chimenti, S., et al. (2001). Bone marrow cells regenerate infarcted myocardium. Nature, 410, 701–705.PubMedGoogle Scholar
  5. 5.
    Losordo, D. W., Henry, T. D., Davidson, C., et al. (2011). Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circulation Research, 109, 428–436.PubMedGoogle Scholar
  6. 6.
    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, 1078–1083.PubMedGoogle Scholar
  7. 7.
    Psaltis, P. J., Zannettino, A. C. W., Worthley, S. G., & Gronthos, S. (2008). Concise review: Mesenchymal stromal cells: Potential for cardiovascular repair. Stem Cells, 26, 2201–2210.PubMedGoogle Scholar
  8. 8.
    Psaltis, P. J., Harbuzariu, A., Delacroix, S., Holroyd, E. W., & Simari, R. D. (2011). Resident vascular progenitor cells–diverse origins, phenotype, and function. Journal of Cardiovascular Translational Research, 4, 161–176.PubMedGoogle Scholar
  9. 9.
    Sabatini, F., Petecchia, L., Tavian, M., Jodon de Villeroche, V., Rossi, G. A., & Brouty-Boye, D. (2005). Human bronchial fibroblasts exhibit a mesenchymal stem cell phenotype and multilineage differentiating potentialities. Laboratory Investigation, 85, 962–971.PubMedGoogle Scholar
  10. 10.
    Zannettino, A. C. W., Paton, S., Arthur, A., et al. (2008). Multipotential human adipose-derived stromal stem cells exhibit a perivascular phenotype in vitro and in vivo. Journal of Cellular Physiology, 214, 413–421.PubMedGoogle Scholar
  11. 11.
    Shi, S., & Gronthos, S. (2003). Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. Journal of Bone and Mineral Research, 18, 696–704.PubMedGoogle Scholar
  12. 12.
    Roufosse, C. A., Direkze, N. C., Otto, W. R., & Wright, N. A. (2004). Circulating mesenchymal stem cells. The International Journal of Biochemistry & Cell Biology, 36, 585–597.Google Scholar
  13. 13.
    Lee, O. K., Kuo, T. K., Chen, W. M., Lee, K. D., Hsieh, S. L., & Chen, T. H. (2004). Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood, 103, 1669–1675.PubMedGoogle Scholar
  14. 14.
    In't Anker, P. S., Scherjon, S. A., Kleijburg-van der Keur, C., et al. (2004). Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells, 22, 1338–1345.Google Scholar
  15. 15.
    Chen, S. L., Fang, W. W., Ye, F., et al. (2004). Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. The American Journal of Cardiology, 94, 92–95.PubMedGoogle Scholar
  16. 16.
    Amado, L. C., Saliaris, A. P., Schuleri, K. H., et al. (2005). Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proceedings of the National Academy of Sciences of the United States of America, 102, 11474–11479.PubMedGoogle Scholar
  17. 17.
    Hare, J. M., Traverse, J. H., Henry, T. D., et al. (2009). A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. Journal of the American College of Cardiology, 54, 2277–2286.PubMedGoogle Scholar
  18. 18.
    Quevedo, H. C., Hatzistergos, K. E., Oskouei, B. N., 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.PubMedGoogle Scholar
  19. 19.
    Psaltis, P. J., Carbone, A., Nelson, A. J., et al. (2010). Reparative effects of allogeneic mesenchymal precursor cells delivered transendocardially in experimental nonischemic cardiomyopathy. JACC. Cardiovascular Interventions, 3, 974–983.PubMedGoogle Scholar
  20. 20.
    Knight, R. L., Booth, C., Wilcox, H. E., Fisher, J., & Ingham, E. (2005). Tissue engineering of cardiac valves: Re-seeding of acellular porcine aortic valve matrices with human mesenchymal progenitor cells. The Journal of Heart Valve Disease, 14, 806–813.PubMedGoogle Scholar
  21. 21.
    Yokokawa, M., Ohnishi, S., Ishibashi-Ueda, H., et al. (2008). Transplantation of mesenchymal stem cells improves atrioventricular conduction in a rat model of complete atrioventricular block. Cell Transplantation, 17, 1145–1155.PubMedGoogle Scholar
  22. 22.
    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, 783–784.PubMedGoogle Scholar
  23. 23.
    Friedenstein, A. J., Chailakhjan, R. K., & Lalykina, K. S. (1970). The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell and Tissue Kinetics, 3, 393–403.PubMedGoogle Scholar
  24. 24.
    Psaltis, P. J., Paton, S., See, F., et al. (2010). Enrichment for STRO-1 expression enhances the cardiovascular paracrine activity of human bone marrow-derived mesenchymal cell populations. Journal of Cellular Physiology, 223, 530–540.PubMedGoogle Scholar
  25. 25.
    Dominici, M., Le Blanc, K., Mueller, I., et al. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8, 315–317.PubMedGoogle Scholar
  26. 26.
    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, 93–98.PubMedGoogle Scholar
  27. 27.
    Gnecchi, M., He, H., Melo, L. G., et al. (2009). Early beneficial effects of bone marrow-derived mesenchymal stem cells overexpressing Akt on cardiac metabolism after myocardial infarction. Stem Cells, 27, 971–979.PubMedGoogle Scholar
  28. 28.
    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, 304–314.PubMedGoogle Scholar
  29. 29.
    Ohnishi, S., Yanagawa, B., Tanaka, K., et al. (2007). Transplantation of mesenchymal stem cells attenuates myocardial injury and dysfunction in a rat model of acute myocarditis. Journal of Molecular and Cellular Cardiology, 42, 88–97.PubMedGoogle Scholar
  30. 30.
    Nagaya, N., Kangawa, K., Itoh, T., et al. (2005). Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy. Circulation, 112, 1128–1135.PubMedGoogle Scholar
  31. 31.
    Van Linthout, S., Savvatis, K., Miteva, K., et al. (2011). Mesenchymal stem cells improve murine acute coxsackievirus B3-induced myocarditis. European Heart Journal, 32(17), 2168–2178.PubMedGoogle Scholar
  32. 32.
    Freyman, T., Polin, G., Osman, H., et al. (2006). A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. European Heart Journal, 27, 1114–1122.PubMedGoogle Scholar
  33. 33.
    Hatzistergos, K. E., Quevedo, H., Oskouei, B. N., et al. (2010). Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation. Circulation Research, 107, 913–922.PubMedGoogle Scholar
  34. 34.
    Kraitchman, D. L., Heldman, A. W., Atalar, E., et al. (2003). In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction. Circulation, 107, 2290–2293.PubMedGoogle Scholar
  35. 35.
    Gyongyosi, M., Blanco, J., Marian, T., et al. (2008). Serial noninvasive in vivo positron emission tomographic tracking of percutaneously intramyocardially injected autologous porcine mesenchymal stem cells modified for transgene reporter gene expression. Circulation. Cardiovascular Imaging, 1, 94–103.PubMedGoogle Scholar
  36. 36.
    Perin, E. C., Tian, M., Marini, F. C., 3rd, et al. (2011). Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model. PLoS One, 6, e22949.PubMedGoogle Scholar
  37. 37.
    Psaltis, P. J., Simari, R. D., & Rodriguez-Porcel, M. (2012). Emerging roles for integrated imaging modalities in cardiovascular cell-based therapeutics: A clinical perspective. European Journal of Nuclear Medicine and Molecular Imaging, 39, 165–181.PubMedGoogle Scholar
  38. 38.
    Silva, G. V., Litovsky, S., Assad, J. A., 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.PubMedGoogle Scholar
  39. 39.
    Schuleri, K. H., Amado, L. C., Boyle, A. J., et al. (2008). Early improvement in cardiac tissue perfusion due to mesenchymal stem cells. American Journal of Physiology - Heart and Circulatory Physiology, 294, H2002–H2011.PubMedGoogle Scholar
  40. 40.
    Arminan, A., Gandia, C., Bartual, M., et al. (2009). Cardiac differentiation is driven by NKX2.5 and GATA4 nuclear translocation in tissue-specific mesenchymal stem cells. Stem Cells and Development, 18, 907–918.PubMedGoogle Scholar
  41. 41.
    Gao, L. R., Zhang, N. K., Bai, J., et al. (2010). The apelin-APJ pathway exists in cardiomyogenic cells derived from mesenchymal stem cells in vitro and in vivo. Cell Transplantation, 19, 949–958.PubMedGoogle Scholar
  42. 42.
    Ge, D., Liu, X., Li, L., et al. (2009). Chemical and physical stimuli induce cardiomyocyte differentiation from stem cells. Biochemical and Biophysical Research Communications, 381, 317–321.PubMedGoogle Scholar
  43. 43.
    Genovese, J. A., Spadaccio, C., Chachques, E., et al. (2009). Cardiac pre-differentiation of human mesenchymal stem cells by electrostimulation. Frontiers in Bioscience, 14, 2996–3002.PubMedGoogle Scholar
  44. 44.
    Makino, S., Fukuda, K., Miyoshi, S., et al. (1999). Cardiomyocytes can be generated from marrow stromal cells in vitro. The Journal of Clinical Investigation, 103, 697–705.PubMedGoogle Scholar
  45. 45.
    Balana, B., Nicoletti, C., Zahanich, I., et al. (2006). 5-Azacytidine induces changes in electrophysiological properties of human mesenchymal stem cells. Cell Research, 16, 949–960.PubMedGoogle Scholar
  46. 46.
    Feng, C., Zhu, J., Zhao, L., et al. (2009). Suberoylanilide hydroxamic acid promotes cardiomyocyte differentiation of rat mesenchymal stem cells. Experimental Cell Research, 315, 3044–3051.PubMedGoogle Scholar
  47. 47.
    Yoon, J., Min, B. G., Kim, Y. H., Shim, W. J., Ro, Y. M., & Lim, D. S. (2005). Differentiation, engraftment and functional effects of pre-treated mesenchymal stem cells in a rat myocardial infarct model. Acta Cardiologica, 60, 277–284.PubMedGoogle Scholar
  48. 48.
    Forte, G., Minieri, M., Cossa, P., et al. (2006). Hepatocyte growth factor effects on mesenchymal stem cells: Proliferation, migration, and differentiation. Stem Cells, 24, 23–33.PubMedGoogle Scholar
  49. 49.
    Li, H., Yu, B., Zhang, Y., Pan, Z., & Xu, W. (2006). Jagged1 protein enhances the differentiation of mesenchymal stem cells into cardiomyocytes. Biochemical and Biophysical Research Communications, 341, 320–325.PubMedGoogle Scholar
  50. 50.
    Herrmann, J. L., Abarbanell, A. M., Weil, B. R., et al. (2010). Postinfarct intramyocardial injection of mesenchymal stem cells pretreated with TGF-alpha improves acute myocardial function. American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 299, R371–R378.PubMedGoogle Scholar
  51. 51.
    Koninckx, R., Hensen, K., Daniels, A., et al. (2009). Human bone marrow stem cells co-cultured with neonatal rat cardiomyocytes display limited cardiomyogenic plasticity. Cytotherapy, 11, 778–792.PubMedGoogle Scholar
  52. 52.
    He, X. Q., Chen, M. S., Li, S. H., et al. (2010). Co-culture with cardiomyocytes enhanced the myogenic conversion of mesenchymal stromal cells in a dose-dependent manner. Molecular and Cellular Biochemistry, 339, 89–98.PubMedGoogle Scholar
  53. 53.
    Labovsky, V., Hofer, E. L., Feldman, L., et al. (2010). Cardiomyogenic differentiation of human bone marrow mesenchymal cells: Role of cardiac extract from neonatal rat cardiomyocytes. Differentiation, 79, 93–101.PubMedGoogle Scholar
  54. 54.
    Nygren, J. M., Jovinge, S., Breitbach, M., et al. (2004). Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nature Medicine, 10, 494–501.PubMedGoogle Scholar
  55. 55.
    Martens, T. P., See, F., Schuster, M. D., et al. (2006). Mesenchymal lineage precursor cells induce vascular network formation in ischemic myocardium. Nature Clinical Practice. Cardiovascular Medicine, 3(Suppl 1), S18–S22.PubMedGoogle Scholar
  56. 56.
    Shake, J. G., Gruber, P. J., Baumgartner, W. A., et al. (2002). Mesenchymal stem cell implantation in a swine myocardial infarct model: Engraftment and functional effects. The Annals of Thoracic Surgery, 73, 1919–1925.PubMedGoogle Scholar
  57. 57.
    Tsuji, H., Miyoshi, S., Ikegami, Y., et al. (2010). Xenografted human amniotic membrane-derived mesenchymal stem cells are immunologically tolerated and transdifferentiated into cardiomyocytes. Circulation Research, 106, 1613–1623.PubMedGoogle Scholar
  58. 58.
    Jumabay, M., Zhang, R., Yao, Y., Goldhaber, J. I., & Bostrom, K. I. (2010). Spontaneously beating cardiomyocytes derived from white mature adipocytes. Cardiovascular Research, 85, 17–27.PubMedGoogle Scholar
  59. 59.
    Gnecchi, M., Zhang, Z., Ni, A., & Dzau, V. J. (2008). Paracrine mechanisms in adult stem cell signaling and therapy. Circulation Research, 103, 1204–1219.PubMedGoogle Scholar
  60. 60.
    Godier-Furnemont, A. F., Martens, T. P., Koeckert, M. S., et al. (2011). Composite scaffold provides a cell delivery platform for cardiovascular repair. Proceedings of the National Academy of Sciences of the United States of America, 108, 7974–7979.PubMedGoogle Scholar
  61. 61.
    Thangarajah, H., Vial, I. N., Chang, E., et al. (2009). IFATS collection: Adipose stromal cells adopt a proangiogenic phenotype under the influence of hypoxia. Stem Cells, 27, 266–274.PubMedGoogle Scholar
  62. 62.
    See, F., Seki, T., Psaltis, P. J., et al. (2010) Therapeutic effects of human STRO-3-selected mesenchymal precursor cells and their soluble factors in experimental myocardial ischemia. Journal of Cellular and Molecular Medicine.Google Scholar
  63. 63.
    Mangi, A. A., Noiseux, N., Kong, D., et al. (2003). Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nature Medicine, 9, 1195–1201.PubMedGoogle Scholar
  64. 64.
    Kinnaird, T., Stabile, E., Burnett, M. 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.PubMedGoogle Scholar
  65. 65.
    Xu, M., Uemura, R., Dai, Y., Wang, Y., Pasha, Z., & Ashraf, M. (2007). In vitro and in vivo effects of bone marrow stem cells on cardiac structure and function. Journal of Molecular and Cellular Cardiology, 42, 441–448.PubMedGoogle Scholar
  66. 66.
    Rogers, T. B., Pati, S., Gaa, S., et al. (2011). Mesenchymal stem cells stimulate protective genetic reprogramming of injured cardiac ventricular myocytes. Journal of Molecular and Cellular Cardiology, 50, 346–356.PubMedGoogle Scholar
  67. 67.
    Benzhi, C., Limei, Z., Ning, W., et al. (2009). Bone marrow mesenchymal stem cells upregulate transient outward potassium currents in postnatal rat ventricular myocytes. Journal of Molecular and Cellular Cardiology, 47, 41–48.PubMedGoogle Scholar
  68. 68.
    Lai, R. C., Arslan, F., Lee, M. M., et al. (2010). Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Research, 4, 214–222.PubMedGoogle Scholar
  69. 69.
    Du, Y. Y., Zhou, S. H., Zhou, T., et al. (2008). Immuno-inflammatory regulation effect of mesenchymal stem cell transplantation in a rat model of myocardial infarction. Cytotherapy, 10, 469–478.PubMedGoogle Scholar
  70. 70.
    Lee, R. H., Pulin, A. A., Seo, M. J., et al. (2009). Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell, 5, 54–63.PubMedGoogle Scholar
  71. 71.
    Ishikane, S., Yamahara, K., Sada, M., et al. (2010). Allogeneic administration of fetal membrane-derived mesenchymal stem cells attenuates acute myocarditis in rats. Journal of Molecular and Cellular Cardiology, 49, 753–761.PubMedGoogle Scholar
  72. 72.
    Li, L., Zhang, S., Zhang, Y., Yu, B., Xu, Y., & Guan, Z. (2009). 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.PubMedGoogle Scholar
  73. 73.
    Dixon, J. A., Gorman, R. C., Stroud, R. E., et al. (2009). Mesenchymal cell transplantation and myocardial remodeling after myocardial infarction. Circulation, 120, S220–S229.PubMedGoogle Scholar
  74. 74.
    Schneider, C., Jaquet, K., Geidel, S., et al. (2009). Transplantation of bone marrow-derived stem cells improves myocardial diastolic function: Strain rate imaging in a model of hibernating myocardium. Journal of the American Society of Echocardiography, 22, 1180–1189.PubMedGoogle Scholar
  75. 75.
    Javazon, E. H., Colter, D. C., Schwarz, E. J., & Prockop, D. J. (2001). Rat marrow stromal cells are more sensitive to plating density and expand more rapidly from single-cell-derived colonies than human marrow stromal cells. Stem Cells, 19, 219–225.PubMedGoogle Scholar
  76. 76.
    Miura, M., Miura, Y., Padilla-Nash, H. M., et al. (2006). Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation. Stem Cells, 24, 1095–1103.PubMedGoogle Scholar
  77. 77.
    Jeong, J. O., Han, J. W., Kim, J. M., et al. (2011). Malignant tumor formation after transplantation of short-term cultured bone marrow mesenchymal stem cells in experimental myocardial infarction and diabetic neuropathy. Circulation Research, 108, 1340–1347.PubMedGoogle Scholar
  78. 78.
    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, 1210–1221.PubMedGoogle Scholar
  79. 79.
    Wollert, K. C., Meyer, G. P., Lotz, J., et al. (2004). Intracoronary autologous bone-marrow cell transfer after myocardial infarction: The BOOST randomised controlled clinical trial. Lancet, 364, 141–148.PubMedGoogle Scholar
  80. 80.
    Lipinski, M. J., Biondi-Zoccai, G. G., Abbate, A., et al. (2007). 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. Journal of the American College of Cardiology, 50, 1761–1767.PubMedGoogle Scholar
  81. 81.
    Pfeffer, M. A., Greaves, S. C., Arnold, J. M. O., et al. (1997). Early versus delayed angiotensin-converting enzyme inhibition therapy in acute myocardial infarction: The healing and early afterload reducing therapy trial. Circulation, 95, 2643–2651.PubMedGoogle Scholar
  82. 82.
    Katritsis, D. G., Sotiropoulou, P. A., Karvouni, E., et al. (2005). Transcoronary transplantation of autologous mesenchymal stem cells and endothelial progenitors into infarcted human myocardium. Catheterization and Cardiovascular Interventions, 65, 321–329.PubMedGoogle Scholar
  83. 83.
    Yang, Z., Zhang, F., Ma, W., et al. (2010). A novel approach to transplanting bone marrow stem cells to repair human myocardial infarction: Delivery via a noninfarct-relative artery. Cardiovascular Therapeutics, 28, 380–385.PubMedGoogle Scholar
  84. 84.
    Chen, S., Liu, Z., Tian, N., et al. (2006). Intracoronary transplantation of autologous bone marrow mesenchymal stem cells for ischemic cardiomyopathy due to isolated chronic occluded left anterior descending artery. The Journal of Invasive Cardiology, 18, 552–556.PubMedGoogle Scholar
  85. 85.
    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, 167–171.PubMedGoogle Scholar
  86. 86.
    Williams, A. R., Trachtenberg, B., Velazquez, D. L., et al. (2011). Intramyocardial stem cell injection in patients with ischemic cardiomyopathy: Functional recovery and reverse remodeling. Circulation Research, 108, 792–796.PubMedGoogle Scholar
  87. 87.
    Di Nicola, M., Carlo-Stella, C., Magni, M., et al. (2002). Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood, 99, 3838–3843.PubMedGoogle Scholar
  88. 88.
    Fischer, U. M., Harting, M. T., Jimenez, F., et al. (2009). Pulmonary passage is a major obstacle for intravenous stem cell delivery: The pulmonary first-pass effect. Stem Cells and Development, 18, 683–692.PubMedGoogle Scholar
  89. 89.
    Nauta, A. J., Westerhuis, G., Kruisselbrink, A. B., Lurvink, E. G., Willemze, R., & Fibbe, W. E. (2006). Donor-derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a nonmyeloablative setting. Blood, 108, 2114–2120.PubMedGoogle Scholar
  90. 90.
    Poncelet, A. J., Vercruysse, J., Saliez, A., & Gianello, P. (2007). Although pig allogeneic mesenchymal stem cells are not immunogenic in vitro, intracardiac injection elicits an immune response in vivo. Transplantation, 83, 783–790.PubMedGoogle Scholar
  91. 91.
    Robey, T. E., Saiget, M. K., Reinecke, H., & Murry, C. E. (2008). Systems approaches to preventing transplanted cell death in cardiac repair. Journal of Molecular and Cellular Cardiology, 45, 567–581.PubMedGoogle Scholar
  92. 92.
    Reinecke, H., Zhang, M., Bartosek, T., & Murry, C. E. (1999). Survival, integration, and differentiation of cardiomyocyte grafts: A study in normal and injured rat hearts. Circulation, 100, 193–202.PubMedGoogle Scholar
  93. 93.
    Simmons, P. J., & Torok-Storb, B. (1991). Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Blood, 78, 55–62.PubMedGoogle Scholar
  94. 94.
    Gronthos, S., Simmons, P. J., Graves, S. E., & Robey, P. G. (2001). Integrin-mediated interactions between human bone marrow stromal precursor cells and the extracellular matrix. Bone, 28, 174–181.PubMedGoogle Scholar
  95. 95.
    Simmons, P. J., Masinovsky, B., Longenecker, B. M., Berenson, R., Torok-Storb, B., & Gallatin, W. M. (1992). Vascular cell adhesion molecule-1 expressed by bone marrow stromal cells mediates the binding of hematopoietic progenitor cells. Blood, 80, 388–395.PubMedGoogle Scholar
  96. 96.
    Sacchetti, B., Funari, A., Michienzi, S., et al. (2007). Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell, 131, 324–336.PubMedGoogle Scholar
  97. 97.
    Quirici, N., Soligo, D., Bossolasco, P., Servida, F., Lumini, C., & Deliliers, G. L. (2002). Isolation of bone marrow mesenchymal stem cells by anti-nerve growth factor receptor antibodies. Experimental Hematology, 30, 783–791.PubMedGoogle Scholar
  98. 98.
    Gronthos, S., & Simmons, P. J. (1995). The growth factor requirements of STRO-1-positive human bone marrow stromal precursors under serum-deprived conditions in vitro. Blood, 85, 929–940.PubMedGoogle Scholar
  99. 99.
    Schwab, K. E., & Gargett, C. E. (2007). Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium. Human Reproduction, 22, 2903–2911.PubMedGoogle Scholar
  100. 100.
    Gronthos, S., Fitter, S., Diamond, P., Simmons, P. J., Itescu, S., & Zannettino, A. C. (2007). A novel monoclonal antibody (STRO-3) identifies an isoform of tissue nonspecific alkaline phosphatase expressed by multipotent bone marrow stromal stem cells. Stem Cells and Development, 16, 953–963.PubMedGoogle Scholar
  101. 101.
    Gronthos, S., McCarty, R., Mrozik, K., et al. (2009). Heat shock protein-90 beta is expressed at the surface of multipotential mesenchymal precursor cells: Generation of a novel monoclonal antibody, STRO-4, with specificity for mesenchymal precursor cells from human and ovine tissues. Stem Cells and Development, 18, 1253–1262.PubMedGoogle Scholar
  102. 102.
    Hamamoto, H., Gorman, J. H., 3rd, Ryan, L. P., et al. (2009). Allogeneic mesenchymal precursor cell therapy to limit remodeling after myocardial infarction: The effect of cell dosage. The Annals of Thoracic Surgery, 87, 794–801.PubMedGoogle Scholar
  103. 103.
    Tondreau, T., Lagneaux, L., Dejeneffe, M., et al. (2004). Isolation of BM mesenchymal stem cells by plastic adhesion or negative selection: Phenotype, proliferation kinetics and differentiation potential. Cytotherapy, 6, 372–379.PubMedGoogle Scholar
  104. 104.
    Lushaj, E. B., Anstadt, E., Haworth, R., et al. (2011). Mesenchymal stromal cells are present in the heart and promote growth of adult stem cells in vitro. Cytotherapy, 13, 400–406.PubMedGoogle Scholar
  105. 105.
    Jiang, Y., Jahagirdar, B., Reinhardt, R., et al. (2002). Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 418, 41–49.PubMedGoogle Scholar
  106. 106.
    Pelacho, B., Nakamura, Y., Zhang, J., et al. (2007). Multipotent adult progenitor cell transplantation increases vascularity and improves left ventricular function after myocardial infarction. Journal of Tissue Engineering and Regenerative Medicine, 1, 51–59.PubMedGoogle Scholar
  107. 107.
    Spees, J. L., Gregory, C. A., Singh, H., et al. (2004). Internalized antigens must be removed to prepare hypoimmunogenic mesenchymal stem cells for cell and gene therapy. Molecular Therapy, 9, 747–756.PubMedGoogle Scholar
  108. 108.
    Crespo-Diaz, R., Behfar, A., Butler, G. W., et al. (2011). Platelet lysate consisting of a natural repair proteome supports human mesenchymal stem cell proliferation and chromosomal stability. Cell Transplantation, 20, 797–811.PubMedGoogle Scholar
  109. 109.
    Hoogduijn, M. J., Crop, M. J., Peeters, A. M., et al. (2009). Donor-derived mesenchymal stem cells remain present and functional in the transplanted human heart. American Journal of Transplantation, 9, 222–230.PubMedGoogle Scholar
  110. 110.
    Bai, X., Yan, Y., Song, Y. H., et al. (2010). Both cultured and freshly isolated adipose tissue-derived stem cells enhance cardiac function after acute myocardial infarction. European Heart Journal, 31, 489–501.PubMedGoogle Scholar
  111. 111.
    Bayes-Genis, A., Soler-Botija, C., Farre, J., et al. (2010). Human progenitor cells derived from cardiac adipose tissue ameliorate myocardial infarction in rodents. Journal of Molecular and Cellular Cardiology, 49, 771–780.PubMedGoogle Scholar
  112. 112.
    Troyer, D. L., & Weiss, M. L. (2008). Wharton’s jelly-derived cells are a primitive stromal cell population. Stem Cells, 26, 591–599.PubMedGoogle Scholar
  113. 113.
    Iop, L., Chiavegato, A., Callegari, A., et al. (2008). Different cardiovascular potential of adult- and fetal-type mesenchymal stem cells in a rat model of heart cryoinjury. Cell Transplantation, 17, 679–694.PubMedGoogle Scholar
  114. 114.
    Kadivar, M., Khatami, S., Mortazavi, Y., Shokrgozar, M. A., Taghikhani, M., & Soleimani, M. (2006). In vitro cardiomyogenic potential of human umbilical vein-derived mesenchymal stem cells. Biochemical and Biophysical Research Communications, 340, 639–647.PubMedGoogle Scholar
  115. 115.
    Gaebel, R., Furlani, D., Sorg, H., et al. (2011). Cell origin of human mesenchymal stem cells determines a different healing performance in cardiac regeneration. PLoS One, 6(2), e15652.PubMedGoogle Scholar
  116. 116.
    Bieback, K., Kern, S., Kluter, H., & Eichler, H. (2004). Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells, 22, 625–634.PubMedGoogle Scholar
  117. 117.
    Schmidt, D., Mol, A., Breymann, C., et al. (2006). Living autologous heart valves engineered from human prenatally harvested progenitors. Circulation, 114, I125–I131.PubMedGoogle Scholar
  118. 118.
    Lee, S. T., White, A. J., Matsushita, S., et al. (2011). Intramyocardial injection of autologous cardiospheres or cardiosphere-derived cells preserves function and minimizes adverse ventricular remodeling in pigs with heart failure post-myocardial infarction. Journal of the American College of Cardiology, 57, 455–465.PubMedGoogle Scholar
  119. 119.
    Gambini, E., Pompilio, G., Biondi, A., et al. (2011). C-kit+cardiac progenitors exhibit mesenchymal markers and preferential cardiovascular commitment. Cardiovascular Research, 89, 362–373.PubMedGoogle Scholar
  120. 120.
    Sethe, S., Scutt, A., & Stolzing, A. (2006). Aging of mesenchymal stem cells. Ageing Research Reviews, 5, 91–116.PubMedGoogle Scholar
  121. 121.
    Tokalov, S. V., Gruner, S., Schindler, S., Wolf, G., Baumann, M., & Abolmaali, N. (2007). Age-related changes in the frequency of mesenchymal stem cells in the bone marrow of rats. Stem Cells and Development, 16, 439–446.PubMedGoogle Scholar
  122. 122.
    Hacia, J. G., Lee, C. C., Jimenez, D. F., et al. (2008). Age-related gene expression profiles of rhesus monkey bone marrow-derived mesenchymal stem cells. Journal of Cellular Biochemistry, 103, 1198–1210.PubMedGoogle Scholar
  123. 123.
    Zhang, H., Fazel, S., Tian, H., et al. (2005). Increasing donor age adversely impacts beneficial effects of bone marrow but not smooth muscle myocardial cell therapy. American Journal of Physiology - Heart and Circulatory Physiology, 289, H2089–H2096.PubMedGoogle Scholar
  124. 124.
    Khan, M., Mohsin, S., Khan, S. N., & Riazuddin, S. (2011). Repair of senescent myocardium by mesenchymal stem cells is dependent on the age of donor mice. Journal of Cellular and Molecular Medicine, 15, 1515–1527.PubMedGoogle Scholar
  125. 125.
    Khan, M., Kwiatkowski, P., Rivera, B. K., & Kuppusamy, P. (2010). Oxygen and oxygenation in stem-cell therapy for myocardial infarction. Life Sciences, 87, 269–274.PubMedGoogle Scholar
  126. 126.
    Kofoed, H., Sjontoft, E., Siemssen, S. O., & Olesen, H. P. (1985). Bone marrow circulation after osteotomy. Blood flow, pO2, pCO2, and pressure studied in dogs. Acta Orthopaedica Scandinavica, 56, 400–403.PubMedGoogle Scholar
  127. 127.
    Hu, X., Yu, S. P., Fraser, J. L., et al. (2008). Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis. The Journal of Thoracic and Cardiovascular Surgery, 135, 799–808.PubMedGoogle Scholar
  128. 128.
    Li, J. H., Zhang, N., & Wang, J. A. (2008). Improved anti-apoptotic and anti-remodeling potency of bone marrow mesenchymal stem cells by anoxic pre-conditioning in diabetic cardiomyopathy. Journal of Endocrinological Investigation, 31, 103–110.PubMedGoogle Scholar
  129. 129.
    Rebelatto, C. K., Aguiar, A. M., Senegaglia, A. C., et al. (2009). Expression of cardiac function genes in adult stem cells is increased by treatment with nitric oxide agents. Biochemical and Biophysical Research Communications, 378, 456–461.PubMedGoogle Scholar
  130. 130.
    Afzal, M. R., Haider, H., Idris, N. M., Jiang, S., Ahmed, R. P., & Ashraf, M. (2010). Pre-conditioning promotes survival and angiomyogenic potential of mesenchymal stem cells in the infarcted heart via NF-kappaB signaling. Antioxidants & Redox Signaling, 12, 693–702.Google Scholar
  131. 131.
    Suzuki, Y., Kim, H. W., Ashraf, M., & Haider, H. (2010). Diazoxide potentiates mesenchymal stem cell survival via NF-kappaB-dependent miR-146a expression by targeting Fas. American Journal of Physiology - Heart and Circulatory Physiology, 299, H1077–H1082.PubMedGoogle Scholar
  132. 132.
    Suzuki, K., Smolenski, R. T., Jayakumar, J., Murtuza, B., Brand, N. J., & Yacoub, M. H. (2000). Heat shock treatment enhances graft cell survival in skeletal myoblast transplantation to the heart. Circulation, 102(19 Suppl 3), III216–III221.PubMedGoogle Scholar
  133. 133.
    Wang, X., Zhao, T., Huang, W., et al. (2009). Hsp20-engineered mesenchymal stem cells are resistant to oxidative stress via enhanced activation of Akt and increased secretion of growth factors. Stem Cells, 27, 3021–3031.PubMedGoogle Scholar
  134. 134.
    Chang, W., Song, B.-W., Lim, S., et al. (2009). Mesenchymal stem cells pretreated with delivered Hph-1-Hsp70 protein are protected from hypoxia-mediated cell death and rescue heart functions from myocardial injury. Stem Cells, 27, 2283–2292.PubMedGoogle Scholar
  135. 135.
    Yang, Y. J., Qian, H. Y., Huang, J., et al. (2009). Combined therapy with simvastatin and bone marrow-derived mesenchymal stem cells increases benefits in infarcted swine hearts. Arteriosclerosis, Thrombosis, and Vascular Biology, 29, 2076–2082.PubMedGoogle Scholar
  136. 136.
    Yang, Y., Mou, Y., Hu, S. J., & Fu, M. (2009). Beneficial effect of rosuvastatin on cardiac dysfunction is associated with alterations in calcium-regulatory proteins. European Journal of Heart Failure, 11, 6–13.PubMedGoogle Scholar
  137. 137.
    Lin, Y. C., Leu, S., Sun, C. K., et al. (2010). Early combined treatment with sildenafil and adipose-derived mesenchymal stem cells preserves heart function in rat dilated cardiomyopathy. Journal of Translational Medicine, 8, 88.PubMedGoogle Scholar
  138. 138.
    Haider, H., Lee, Y. J., Jiang, S., Ahmed, R. P., Ryon, M., & Ashraf, M. (2010). Phosphodiesterase inhibition with tadalafil provides longer and sustained protection of stem cells. American Journal of Physiology - Heart and Circulatory Physiology, 299, H1395–H1404.PubMedGoogle Scholar
  139. 139.
    Numasawa, Y., Kimura, T., Miyoshi, S., et al. (2011). Treatment of human mesenchymal stem cells with angiotensin receptor blocker improved efficiency of cardiomyogenic transdifferentiation and improved cardiac function via angiogenesis. Stem Cells, 29, 1405–1414.PubMedGoogle Scholar
  140. 140.
    Wang, Y., Zhang, D., Ashraf, M., et al. (2010). Combining neuropeptide Y and mesenchymal stem cells reverses remodeling after myocardial infarction. American Journal of Physiology - Heart and Circulatory Physiology, 298, H275–H286.PubMedGoogle Scholar
  141. 141.
    Kinnaird, T., Stabile, E., Burnett, M. S., et al. (2004). Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation, 109, 1543–1549.PubMedGoogle Scholar
  142. 142.
    Herrmann, J. L., Wang, Y., Abarbanell, A. M., Weil, B. R., Tan, J., & Meldrum, D. R. (2010). Pre-conditioning mesenchymal stem cells with transforming growth factor-alpha improves mesenchymal stem cell-mediated cardioprotection. Shock, 33, 24–30.PubMedGoogle Scholar
  143. 143.
    Pasha, Z., Wang, Y., Sheikh, R., Zhang, D., Zhao, T., & Ashraf, M. (2008). Pre-conditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium. Cardiovascular Research, 77, 134–142.PubMedGoogle Scholar
  144. 144.
    Yao, Y., Zhang, F., Wang, L., et al. (2009). Lipopolysaccharide pre-conditioning enhances the efficacy of mesenchymal stem cells transplantation in a rat model of acute myocardial infarction. Journal of Biomedical Science, 16, 74.PubMedGoogle Scholar
  145. 145.
    Matsumoto, R., Omura, T., Yoshiyama, M., et al. (2005). Vascular endothelial growth factor–expressing mesenchymal stem cell transplantation for the treatment of acute myocardial infarction. Arteriosclerosis, Thrombosis, and Vascular Biology, 25, 1168–1173.PubMedGoogle Scholar
  146. 146.
    Guo, J., Lin, G., Bao, C., Hu, Z., Chu, H., & Hu, M. (2008). Insulin-like growth factor 1 improves the efficacy of mesenchymal stem cells transplantation in a rat model of myocardial infarction. Journal of Biomedical Science, 15, 89–97.PubMedGoogle Scholar
  147. 147.
    Abbott, J. D., Huang, Y., Liu, D., Hickey, R., Krause, D. S., & Giordano, F. J. (2004). Stromal cell–derived factor-1α plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury. Circulation, 110, 3300–3305.PubMedGoogle Scholar
  148. 148.
    Kijowski, J., Baj-Krzyworzeka, M., Majka, M., et al. (2001). The SDF-1-CXCR4 axis stimulates VEGF secretion and activates integrins but does not affect proliferation and survival in lymphohematopoietic cells. Stem Cells, 19, 453–466.PubMedGoogle Scholar
  149. 149.
    Zhuang, Y., Chen, X., Xu, M., Zhang, L. Y., & Xiang, F. (2009). Chemokine stromal cell-derived factor 1/CXCL12 increases homing of mesenchymal stem cells to injured myocardium and neovascularization following myocardial infarction. Chinese Medical Journal, 122, 183–187.PubMedGoogle Scholar
  150. 150.
    Tang, J., Wang, J., Guo, L., et al. (2010). Mesenchymal stem cells modified with stromal cell-derived factor 1 alpha improve cardiac remodeling via paracrine activation of hepatocyte growth factor in a rat model of myocardial infarction. Molecules and Cells, 29, 9–19.PubMedGoogle Scholar
  151. 151.
    Guo, Y. H., He, J. G., Wu, J. L., et al. (2008). Hepatocyte growth factor and granulocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy. Cytotherapy, 10, 857–867.PubMedGoogle Scholar
  152. 152.
    Huang, J., Zhang, Z., Guo, J., et al. (2010). Genetic modification of mesenchymal stem cells overexpressing CCR1 increases cell viability, migration, engraftment, and capillary density in the injured myocardium. Circulation Research, 106, 1753–1762.PubMedGoogle Scholar
  153. 153.
    Tang, J., Wang, J., Zheng, F., et al. (2010). Combination of chemokine and angiogenic factor genes and mesenchymal stem cells could enhance angiogenesis and improve cardiac function after acute myocardial infarction in rats. Molecular and Cellular Biochemistry, 339, 107–118.PubMedGoogle Scholar
  154. 154.
    Franke, T. F., Kaplan, D. R., & Cantley, L. C. (1997). PI3K: Downstream AKTion blocks apoptosis. Cell, 88, 435–437.PubMedGoogle Scholar
  155. 155.
    Datta, S. R., Brunet, A., & Greenberg, M. E. (1999). Cellular survival: A play in three Akts. Genes & Development, 13, 2905–2927.Google Scholar
  156. 156.
    Somanath, P. R., Razorenova, O. V., Chen, J., & Byzova, T. V. (2006). Akt1 in endothelial cell and angiogenesis. Cell Cycle, 5, 512–518.PubMedGoogle Scholar
  157. 157.
    Gnecchi, M., He, H., Liang, O. D., et al. (2005). Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nature Medicine, 11, 367–368.PubMedGoogle Scholar
  158. 158.
    Gnecchi, M., He, H., Noiseux, N., et al. (2006). Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. The FASEB Journal, 20, 661–669.Google Scholar
  159. 159.
    Mirotsou, M., Zhang, Z., Deb, A., et al. (2007). Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair. Proceedings of the National Academy of Sciences of the United States of America, 104, 1643–1648.PubMedGoogle Scholar
  160. 160.
    Song, S. W., Chang, W., Song, B. W., et al. (2009). Integrin-linked kinase is required in hypoxic mesenchymal stem cells for strengthening cell adhesion to ischemic myocardium. Stem Cells, 27, 1358–1365.PubMedGoogle Scholar
  161. 161.
    Jiang, Y., Chen, L., Tang, Y., et al. (2010). HO-1 gene overexpression enhances the beneficial effects of superparamagnetic iron oxide labeled bone marrow stromal cells transplantation in swine hearts underwent ischemia/reperfusion: An MRI study. Basic Research in Cardiology, 105, 431–442.PubMedGoogle Scholar
  162. 162.
    Taljaard, M., Ward, M. R., Kutryk, M. J., et al. (2010). Rationale and design of Enhanced Angiogenic Cell Therapy in Acute Myocardial Infarction (ENACT-AMI): The first randomized placebo-controlled trial of enhanced progenitor cell therapy for acute myocardial infarction. American Heart Journal, 159, 354–360.PubMedGoogle Scholar
  163. 163.
    Mias, C., Trouche, E., Seguelas, M. H., et al. (2008). Ex vivo pretreatment with melatonin improves survival, proangiogenic/mitogenic activity, and efficiency of mesenchymal stem cells injected into ischemic kidney. Stem Cells, 26, 1749–1757.PubMedGoogle Scholar
  164. 164.
    Behfar, A., Zingman, L. V., Hodgson, D. M., et al. (2002). Stem cell differentiation requires a paracrine pathway in the heart. The FASEB Journal, 16, 1558–1566.Google Scholar
  165. 165.
    Behfar, A., Perez-Terzic, C., Faustino, R. S., et al. (2007). Cardiopoietic programming of embryonic stem cells for tumor-free heart repair. The Journal of Experimental Medicine, 204, 405–420.PubMedGoogle Scholar
  166. 166.
    Behfar, A., Yamada, S., Crespo-Diaz, R., 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.PubMedGoogle Scholar
  167. 167.
    Bartunek, J., Wijns, W., Dolatabadi, D., et al. (2011). C-cure multicenter trial: Lineage specific bone marrow derived cardiopoietic mesenchymal stem cells for the treatment of ischaemic cardiomyopathy. Journal of the American College of Cardiology, 57, E200. Abstract.Google Scholar
  168. 168.
    Yang, Y.-J., Qian, H.-Y., Huang, J., et al. (2008). Atorvastatin treatment improves survival and effects of implanted mesenchymal stem cells in post-infarct swine hearts. European Heart Journal, 29, 1578–1590.PubMedGoogle Scholar
  169. 169.
    Xu, R., Chen, J., Cong, X., Hu, S., & Chen, X. (2008). Lovastatin protects mesenchymal stem cells against hypoxia- and serum deprivation-induced apoptosis by activation of PI3K/Akt and ERK1/2. Journal of Cellular Biochemistry, 103, 256–269.PubMedGoogle Scholar
  170. 170.
    Khan, M., Meduru, S., Mohan, I. K., et al. (2009). Hyperbaric oxygenation enhances transplanted cell graft and functional recovery in the infarct heart. Journal of Molecular and Cellular Cardiology, 47, 275–287.PubMedGoogle Scholar
  171. 171.
    Zhang, H., Hou, J. F., Shen, Y., Wang, W., Wei, Y. J., & Hu, S. (2010). Low level laser irradiation precondition to create friendly milieu of infarcted myocardium and enhance early survival of transplanted bone marrow cells. Journal of Cellular and Molecular Medicine, 14, 1975–1987.PubMedGoogle Scholar
  172. 172.
    Briones, E., Lacalle, J. R., Marin, I. (2009) Transmyocardial laser revascularization versus medical therapy for refractory angina. Cochrane Database of Systematic Reviews CD003712.Google Scholar
  173. 173.
    Psaltis, P. J., & Worthley, S. G. (2009). Endoventricular electromechanical mapping-the diagnostic and therapeutic utility of the NOGA XP Cardiac Navigation System. Journal of Cardiovascular Translational Research, 2, 48–62.PubMedGoogle Scholar
  174. 174.
    Reyes, G., Allen, K. B., Alvarez, P., et al. (2010). Midterm results after bone marrow laser revascularization for treating refractory angina. BMC Cardiovascular Disorders, 10, 42.PubMedGoogle Scholar
  175. 175.
    Traverse, J. H., Henry, T. D., Ellis, S. G., et al. (2011). Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: The LateTIME randomized trial. Journal of the American Medical Association, 306, 2110–2119.PubMedGoogle Scholar
  176. 176.
    Ly, H. Q., Hoshino, K., Pomerantseva, I., et al. (2009). In vivo myocardial distribution of multipotent progenitor cells following intracoronary delivery in a swine model of myocardial infarction. European Heart Journal, 30, 2861–2868.PubMedGoogle Scholar
  177. 177.
    Hou, D., Youssef, E. A., Brinton, T. J., et al. (2005). Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: Implications for current clinical trials. Circulation, 112, I150–I156.PubMedGoogle Scholar
  178. 178.
    Perin, E. C., Silva, G. V., Assad, J. A., et al. (2008). Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction. Journal of Molecular and Cellular Cardiology, 44, 486–495.PubMedGoogle Scholar
  179. 179.
    Mitchell, A. J., Sabondjian, E., Sykes, J., et al. (2010). Comparison of initial cell retention and clearance kinetics after subendocardial or subepicardial injections of endothelial progenitor cells in a canine myocardial infarction model. Journal of Nuclear Medicine, 51, 413–417.PubMedGoogle Scholar
  180. 180.
    Psaltis, P., Zannettino, A., Gronthos, S., & Worthley, S. (2010). Intramyocardial navigation and mapping for stem cell delivery. Journal of Cardiovascular Translational Research, 3, 135–146.PubMedGoogle Scholar
  181. 181.
    Christman, K. L., Vardanian, A. J., Fang, Q., Sievers, R. E., Fok, H. H., & Lee, R. J. (2004). Injectable fibrin scaffold improves cell transplant survival, reduces infarct expansion, and induces neovasculature formation in ischemic myocardium. Journal of the American College of Cardiology, 44, 654–660.PubMedGoogle Scholar
  182. 182.
    Leor, J., Amsalem, Y., & Cohen, S. (2005). Cells, scaffolds, and molecules for myocardial tissue engineering. Pharmacology and Therapeutics, 105, 151–163.PubMedGoogle Scholar
  183. 183.
    Kofidis, T., Lebl, D. R., Martinez, E. C., Hoyt, G., Tanaka, M., & Robbins, R. C. (2005). Novel injectable bioartificial tissue facilitates targeted, less invasive, large-scale tissue restoration on the beating heart after myocardial injury. Circulation, 112(9 Suppl), I173–I177.PubMedGoogle Scholar
  184. 184.
    Terrovitis, J., Lautamaki, R., Bonios, M., et al. (2009). Noninvasive quantification and optimization of acute cell retention by in vivo positron emission tomography after intramyocardial cardiac-derived stem cell delivery. Journal of the American College of Cardiology, 54, 1619–1626.PubMedGoogle Scholar
  185. 185.
    Davis, M. E., Motion, J. P. M., Narmoneva, D. A., et al. (2005). Injectable self-assembling peptide nanofibers create intramyocardial microenvironments for endothelial cells. Circulation, 111, 442–450.PubMedGoogle Scholar
  186. 186.
    Segers, V. F., Tokunou, T., Higgins, L. J., MacGillivray, C., Gannon, J., & Lee, R. T. (2007). Local delivery of protease-resistant stromal cell derived factor-1 for stem cell recruitment after myocardial infarction. Circulation, 116, 1683–1692.PubMedGoogle Scholar
  187. 187.
    Barnett, B. P., Ruiz-Cabello, J., Hota, P., et al. (2011). Fluorocapsules for improved function, immunoprotection, and visualization of cellular therapeutics with MR, US, and CT imaging. Radiology, 258, 182–191.PubMedGoogle Scholar
  188. 188.
    Melero-Martin, J. M., De Obaldia, M. E., Kang, S. Y., et al. (2008). Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells. Circulation Research, 103, 194–202.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • James D. Richardson
    • 1
  • Adam J. Nelson
    • 1
  • Andrew C. W. Zannettino
    • 2
  • Stan Gronthos
    • 2
  • Stephen G. Worthley
    • 1
  • Peter J. Psaltis
    • 1
    • 3
  1. 1.Cardiovascular Research Centre, Royal Adelaide Hospital and Department of MedicineUniversity of AdelaideAdelaideAustralia
  2. 2.Department of Haematology, SA Pathology and Centre for Stem Cell Research, Robinson Institute, Discipline of MedicineUniversity of AdelaideAdelaideAustralia
  3. 3.Division of Cardiovascular DiseasesMayo ClinicRochesterUSA

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