Skip to main content
Log in

Review of Stem Cell-Based Therapy for the Treatment of Cardiovascular Disease

  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

Cardiovascular disease remains the number one cause of mortality in the United States. Nearly 2,400 Americans die of cardiovascular disease each day, an average of 1 every 37 s [1]. One in three Americans has been diagnosed with one or more forms of cardiovascular disease. Most recent estimates show that, in the United States alone, 16 million people have coronary artery disease and 5.3 million have been diagnosed with heart failure. Unlike other forms of cardiovascular disease, heart failure is often the end-stage of a cardiovascular disease, frequently coronary artery disease. The 1-year mortality of people diagnosed with heart failure remains a sobering 20%. Heart failure is also very costly. The estimated direct and indirect cost of heart failure in the US for 2008 is 34.8 billion dollars [1]. Therefore, advanced treatment options for these populations could greatly impact patient health outcomes and cost savings. Even with the advancements in pharmacologic therapies and improvements in mechanical support devices, the only definitive treatment for advanced heart failure remains heart transplantation. Given the limited availability of donor organs for use in orthotopic heart transplantation, alternative therapies including stem cell-based therapies have been explored. The past decade has seen an explosion of activity of the field of cardiac regeneration. New scientific techniques and discoveries have allowed rapid advancements but there have also been conflicting opinions and results. The concept of cardiac regeneration is now commonly accepted but the exact mechanisms and extent of regeneration is greatly debated. Several candidate cell populations, both cardiac and extracardiac, have been reported to be capable of cardiac regeneration [210]. However, some studies question if these cell populations actually differentiate into cardiomyocytes but rather function through paracrine effects or through cell fusion [1113, 1419]. Despite these challenges, the field has also begun translating the preclinical animal studies into human clinical trials using several cell types for the treatment of many clinical disease states. This review will highlight the preclinical animal studies and review the results of the published clinical trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Rosamond, W., et al. (2008). Heart disease and stroke statistics—2008 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation, 117(4), e25–e146.

    PubMed  Google Scholar 

  2. Bittner, R. E., et al. (1999). Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice. Anatomy and Embryology (Berlin), 199(5), 391–396.

    CAS  Google Scholar 

  3. Jackson, K. A., et al. (2001). Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. Journal of Clinical Investigation, 107(11), 1395–1402.

    PubMed  CAS  Google Scholar 

  4. Orlic, D., et al. (2001). Bone marrow cells regenerate infarcted myocardium. Nature, 410(6829), 701–705.

    PubMed  CAS  Google Scholar 

  5. Orlic, D., et al. (2001). Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proceedings of the National Academy of Sciences of the United States of America, 98(18), 10344–10349.

    PubMed  CAS  Google Scholar 

  6. Beltrami, A. P., et al. (2003). Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell, 114(6), 763–776.

    PubMed  CAS  Google Scholar 

  7. Oh, H., 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(21), 12313–12318.

    PubMed  CAS  Google Scholar 

  8. Martin, C. M., 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(1), 262–275.

    Article  CAS  Google Scholar 

  9. Messina, E., et al. (2004). Isolation and expansion of adult cardiac stem cells from human and murine heart. Circulation Research, 95(9), 911–921.

    PubMed  CAS  Google Scholar 

  10. Laugwitz, K. L., et al. (2005). Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature, 433(7026), 647–653.

    PubMed  CAS  Google Scholar 

  11. Gnecchi, M., et al. (2005). Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nature Medicine, 11(4), 367–368.

    PubMed  CAS  Google Scholar 

  12. Kinnaird, T., 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(5), 678–685.

    PubMed  CAS  Google Scholar 

  13. Uemura, R., et al. (2006). Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. Circulation Research, 98(11), 1414–1421.

    PubMed  CAS  Google Scholar 

  14. Balsam, L. B., et al. (2004). Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature, 428(6983), 668–673.

    PubMed  CAS  Google Scholar 

  15. Murry, C. E., et al. (2004). Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature, 428(6983), 664–668.

    PubMed  CAS  Google Scholar 

  16. Nygren, J. M., et al. (2004). Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nature Medicine, 10(5), 494–501.

    PubMed  CAS  Google Scholar 

  17. Alvarez-Dolado, M., et al. (2003). Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature, 425(6961), 968–973.

    PubMed  CAS  Google Scholar 

  18. Terada, N., et al. (2002). Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature, 416(6880), 542–545.

    PubMed  CAS  Google Scholar 

  19. Ying, Q. L., et al. (2002). Changing potency by spontaneous fusion. Nature, 416(6880), 545–548.

    PubMed  CAS  Google Scholar 

  20. Evans, M. J., & Kaufman, M. H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature, 292(5819), 154–156.

    PubMed  CAS  Google Scholar 

  21. Doetschman, T. C., et al. (1985). The in vitro development of blastocyst-derived embryonic stem cell lines: Formation of visceral yolk sac, blood islands and myocardium. Journal of Embryology and Experimental Morphology, 87, 27–45.

    PubMed  CAS  Google Scholar 

  22. Boheler, K. R., et al. (2002). Differentiation of pluripotent embryonic stem cells into cardiomyocytes. Circulation Research, 91(3), 189–201.

    PubMed  CAS  Google Scholar 

  23. Heng, B. C., et al. (2004). Strategies for directing the differentiation of stem cells into the cardiomyogenic lineage in vitro. Cardiovascular Research, 62(1), 34–42.

    PubMed  CAS  Google Scholar 

  24. Sachinidis, A., et al. (2003). Cardiac specific differentiation of mouse embryonic stem cells. Cardiovascular Research, 58(2), 278–291.

    PubMed  CAS  Google Scholar 

  25. Klug, M. G., et al. (1996). Genetically selected cardiomyocytes from differentiating embryonic stem cells form stable intracardiac grafts. Journal of Clinical Investigation, 98(1), 216–224.

    PubMed  CAS  Google Scholar 

  26. Behfar, A., et al. (2002). Stem cell differentiation requires a paracrine pathway in the heart. FASEB Journal, 16(12), 1558–1566.

    PubMed  Google Scholar 

  27. Min, J. Y., et al. (2002). Transplantation of embryonic stem cells improves cardiac function in postinfarcted rats. Journal of Applied Physiology, 92(1), 288–296.

    PubMed  Google Scholar 

  28. Yang, Y., et al. (2002). VEGF enhances functional improvement of postinfarcted hearts by transplantation of ESC-differentiated cells. Journal of Applied Physiology, 93(3), 1140–1151.

    PubMed  CAS  Google Scholar 

  29. Kolossov, E., et al. (2006). Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium. Journal of Experimental Medicine, 203(10), 2315–2327.

    PubMed  CAS  Google Scholar 

  30. Vittet, D., et al. (1996). Embryonic stem cells differentiate in vitro to endothelial cells through successive maturation steps. Blood, 88(9), 3424–3431.

    PubMed  CAS  Google Scholar 

  31. Yamashita, J., et al. (2000). Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors. Nature, 408(6808), 92–96.

    PubMed  CAS  Google Scholar 

  32. Marchetti, S., et al. (2002). Endothelial cells genetically selected from differentiating mouse embryonic stem cells incorporate at sites of neovascularization in vivo. Journal of Cell Science, 115(Pt 10), 2075–2085.

    PubMed  CAS  Google Scholar 

  33. Thomson, J. A., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282(5391), 1145–1147.

    PubMed  CAS  Google Scholar 

  34. He, J. Q., et al. (2003). Human embryonic stem cells develop into multiple types of cardiac myocytes: Action potential characterization. Circulation Research, 93(1), 32–39.

    PubMed  CAS  Google Scholar 

  35. Kehat, I., et al. (2001). Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. Journal Clinical Investigation, 108(3), 407–414.

    CAS  Google Scholar 

  36. Laflamme, M. A., et al. (2005). Formation of human myocardium in the rat heart from human embryonic stem cells. American Journal of Pathology, 167(3), 663–671.

    PubMed  CAS  Google Scholar 

  37. McDevitt, T. C., Laflamme, M. A., & Murry, C. E. (2005). Proliferation of cardiomyocytes derived from human embryonic stem cells is mediated via the IGF/PI 3-kinase/Akt signaling pathway. Journal of Molecular and Cellular Cardiology, 39(6), 865–873.

    PubMed  CAS  Google Scholar 

  38. Murry, C. E., Field, L. J., & Menasche, P. (2005). Cell-based cardiac repair: Reflections at the 10-year point. Circulation, 112(20), 3174–3183.

    PubMed  Google Scholar 

  39. Chiu, R. C., Zibaitis, A., & Kao, R. L. (1995). Cellular cardiomyoplasty: Myocardial regeneration with satellite cell implantation. Annals of Thoracic Surgery, 60(1), 12–18.

    PubMed  CAS  Google Scholar 

  40. Jain, M., et al. (2001). Cell therapy attenuates deleterious ventricular remodeling and improves cardiac performance after myocardial infarction. Circulation, 103(14), 1920–1927.

    PubMed  CAS  Google Scholar 

  41. Murry, C. E., et al. (1996). Skeletal myoblast transplantation for repair of myocardial necrosis. Journal of Clinical Investigation, 98(11), 2512–2523.

    PubMed  CAS  Google Scholar 

  42. Rajnoch, C., et al. (2001). Cellular therapy reverses myocardial dysfunction. Journal of Thoracic and Cardiovascular Surgery, 121(5), 871–878.

    PubMed  CAS  Google Scholar 

  43. Scorsin, M., et al. (2000). Comparison of the effects of fetal cardiomyocyte and skeletal myoblast transplantation on postinfarction left ventricular function. Journal of Thoracic and Cardiovascular Surgery, 119(6), 1169–1175.

    PubMed  CAS  Google Scholar 

  44. Taylor, D. A., et al. (1998). Regenerating functional myocardium: Improved performance after skeletal myoblast transplantation. Nature Medicine, 4(8), 929–933.

    PubMed  CAS  Google Scholar 

  45. Leobon, B., et al. (2003). Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host. Proceedings of the National Academy of Sciences of the United States of America, 100(13), 7808–7811.

    PubMed  CAS  Google Scholar 

  46. Reinecke, H., et al. (2000). Electromechanical coupling between skeletal and cardiac muscle. Implications for infarct repair. Journal of Cell Biology, 149(3), 731–740.

    PubMed  CAS  Google Scholar 

  47. Reinecke, H., Poppa, V., & Murry, C. E. (2002). Skeletal muscle stem cells do not transdifferentiate into cardiomyocytes after cardiac grafting. Journal of Molecular and Cellular Cardiology, 34(2), 241–249.

    PubMed  CAS  Google Scholar 

  48. Cleland, J. G., et al. (2007). Clinical trials update from the American Heart Association 2006: OAT, SALT 1 and 2, MAGIC, ABCD, PABA-CHF, IMPROVE-CHF, and percutaneous mitral annuloplasty. European Journal of Heart Failure, 9(1), 92–97.

    PubMed  CAS  Google Scholar 

  49. Young, P. P., Vaughan, D. E., & Hatzopoulos, A. K. (2007). Biologic properties of endothelial progenitor cells and their potential for cell therapy. Progress in Cardiovascular Diseases, 49(6), 421–429.

    PubMed  CAS  Google Scholar 

  50. Kawamoto, A., et al. (2001). Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation, 103(5), 634–637.

    PubMed  CAS  Google Scholar 

  51. Kawamoto, A., et al. (2003). Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia. Circulation, 107(3), 461–468.

    PubMed  Google Scholar 

  52. Kocher, A. A., et al. (2001). Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nature Medicine, 7(4), 430–436.

    PubMed  CAS  Google Scholar 

  53. Schuster, M. D., et al. (2004). Myocardial neovascularization by bone marrow angioblasts results in cardiomyocyte regeneration. American Journal of Physiology. Heart and Circulatory Physiology, 287(2), H525–H532.

    PubMed  CAS  Google Scholar 

  54. Badorff, C., et al. (2003). Transdifferentiation of blood-derived human adult endothelial progenitor cells into functionally active cardiomyocytes. Circulation, 107(7), 1024–1032.

    PubMed  Google Scholar 

  55. Condorelli, G., et al. (2001). Cardiomyocytes induce endothelial cells to trans-differentiate into cardiac muscle: Implications for myocardium regeneration. Proceedings of the National Academy of Sciences of the United States of America, 98(19), 10733–10738.

    PubMed  CAS  Google Scholar 

  56. Gruh, I., et al. (2006). No evidence of transdifferentiation of human endothelial progenitor cells into cardiomyocytes after coculture with neonatal rat cardiomyocytes. Circulation, 113(10), 1326–1334.

    PubMed  CAS  Google Scholar 

  57. Koyanagi, M., et al. (2005). Differentiation of circulating endothelial progenitor cells to a cardiomyogenic phenotype depends on E-cadherin. FEBS Letters, 579(27), 6060–6066.

    PubMed  CAS  Google Scholar 

  58. Zimmet, J. M., & Hare, J. M. (2005). Emerging role for bone marrow derived mesenchymal stem cells in myocardial regenerative therapy. Basic Research in Cardiology, 100(6), 471–481.

    PubMed  CAS  Google Scholar 

  59. Haynesworth, S. E., Baber, M. A., & Caplan, A. I. (1992). Cell surface antigens on human marrow-derived mesenchymal cells are detected by monoclonal antibodies. Bone, 13(1), 69–80.

    PubMed  CAS  Google Scholar 

  60. Majumdar, M. K., et al. (2003). Characterization and functionality of cell surface molecules on human mesenchymal stem cells. Journal of Biomedical Science, 10(2), 228–241.

    PubMed  CAS  Google Scholar 

  61. Pittenger, M. F., & Martin, B. J. (2004). Mesenchymal stem cells and their potential as cardiac therapeutics. Circulation Research, 95(1), 9–20.

    PubMed  CAS  Google Scholar 

  62. Pittenger, M. F., et al. (1999). Multilineage potential of adult human mesenchymal stem cells. Science, 284(5411), 143–147.

    PubMed  CAS  Google Scholar 

  63. Tomita, S., et al. (1999). Autologous transplantation of bone marrow cells improves damaged heart function. Circulation, 100(19 Suppl), II247–II256.

    PubMed  CAS  Google Scholar 

  64. Toma, C., et al. (2002). Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation, 105(1), 93–98.

    PubMed  Google Scholar 

  65. Wang, J. S., et al. (2000). Marrow stromal cells for cellular cardiomyoplasty: Feasibility and potential clinical advantages. Journal of Thoracic and Cardiovascular Surgery, 120(5), 999–1005.

    PubMed  CAS  Google Scholar 

  66. Shake, J. G., et al. (2002). Mesenchymal stem cell implantation in a swine myocardial infarct model: Engraftment and functional effects. Annals of Thoracic Surgery, 73(6), 1919–1925 discussion 1926.

    PubMed  Google Scholar 

  67. Gojo, S., et al. (2003). In vivo cardiovasculogenesis by direct injection of isolated adult mesenchymal stem cells. Experimental Cell Research, 288(1), 51–59.

    PubMed  CAS  Google Scholar 

  68. Bartunek, J., et al. (2007). Pretreatment of adult bone marrow mesenchymal stem cells with cardiomyogenic growth factors and repair of the chronically infarcted myocardium. American Journal of Physiology. Heart and Circulatory Physiology, 292(2), H1095–H1104.

    PubMed  CAS  Google Scholar 

  69. Hattan, N., et al. (2005). Purified cardiomyocytes from bone marrow mesenchymal stem cells produce stable intracardiac grafts in mice. Cardiovascular Research, 65(2), 334–344.

    PubMed  CAS  Google Scholar 

  70. Vulliet, P. R., et al. (2004). Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet, 363(9411), 783–784.

    PubMed  Google Scholar 

  71. Amado, L. C., 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(32), 11474–11479.

    PubMed  CAS  Google Scholar 

  72. Jiang, X. X., et al. (2005). Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood, 105(10), 4120–4126.

    PubMed  CAS  Google Scholar 

  73. Strauer, B. E., et al. (2002). Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation, 106(15), 1913–1918.

    PubMed  Google Scholar 

  74. Assmus, B., et al. (2002). Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation, 106(24), 3009–3017.

    PubMed  Google Scholar 

  75. Dobert, N., et al. (2004). Transplantation of progenitor cells after reperfused acute myocardial infarction: Evaluation of perfusion and myocardial viability with FDG-PET and thallium SPECT. European Journal of Nuclear Medicine and Molecular Imaging, 31(8), 1146–1151.

    PubMed  Google Scholar 

  76. Schachinger, V., et al. (2004). Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: Final one-year results of the TOPCARE-AMI Trial. Journal of the American College of Cardiology, 44(8), 1690–1699.

    PubMed  Google Scholar 

  77. Wollert, K. C., et al. (2004). Intracoronary autologous bone-marrow cell transfer after myocardial infarction: The BOOST randomised controlled clinical trial. Lancet, 364(9429), 141–148.

    PubMed  Google Scholar 

  78. Meyer, G. P., et al. (2006). Intracoronary bone marrow cell transfer after myocardial infarction: Eighteen months’ follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial. Circulation, 113(10), 1287–1294.

    PubMed  Google Scholar 

  79. Lunde, K., et al. (2006). Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. New England Journal of Medicine, 355(12), 1199–1209.

    PubMed  CAS  Google Scholar 

  80. Schachinger, V., et al. (2006). Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. New England Journal of Medicine, 355(12), 1210–1221.

    PubMed  CAS  Google Scholar 

  81. Janssens, S., et al. (2006). Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: Double-blind, randomised controlled trial. Lancet, 367(9505), 113–121.

    PubMed  Google Scholar 

  82. Ince, H., et al. (2005). Preservation from left ventricular remodeling by front-integrated revascularization and stem cell liberation in evolving acute myocardial infarction by use of granulocyte-colony-stimulating factor (FIRSTLINE-AMI). Circulation, 112(20), 3097–3106.

    PubMed  CAS  Google Scholar 

  83. Engelmann, M. G., et al. (2006). Autologous bone marrow stem cell mobilization induced by granulocyte colony-stimulating factor after subacute ST-segment elevation myocardial infarction undergoing late revascularization: Final results from the G-CSF-STEMI (Granulocyte Colony-Stimulating Factor ST-Segment Elevation Myocardial Infarction) trial. Journal of the American College of Cardiology, 48(8), 1712–1721.

    PubMed  CAS  Google Scholar 

  84. Ripa, R. S., et al. (2006). Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: Result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial. Circulation, 113(16), 1983–1992.

    PubMed  CAS  Google Scholar 

  85. Zohlnhofer, D., et al. (2006). Stem cell mobilization by granulocyte colony-stimulating factor in patients with acute myocardial infarction: A randomized controlled trial. JAMA, 295(9), 1003–1010.

    PubMed  Google Scholar 

  86. Ince, H., et al. (2005). Prevention of left ventricular remodeling with granulocyte colony-stimulating factor after acute myocardial infarction: Final 1-year results of the front-integrated revascularization and stem cell liberation in evolving acute myocardial infarction by granulocyte colony-stimulating factor (FIRSTLINE-AMI) trial. Circulation, 112(9 Suppl), I73–180.

    PubMed  Google Scholar 

  87. Kang, H. J., et al. (2007). Intracoronary infusion of the mobilized peripheral blood stem cell by G-CSF is better than mobilization alone by G-CSF for improvement of cardiac function and remodeling: 2-year follow-up results of the myocardial regeneration and angiogenesis in myocardial infarction with G-CSF and intra-coronary stem cell infusion (MAGIC Cell) 1 trial. American Heart Journal, 153(2), 237 e1–e8.

    Google Scholar 

  88. Kang, H. J., et al. (2004). Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: The MAGIC cell randomised clinical trial. Lancet, 363(9411), 751–756.

    PubMed  CAS  Google Scholar 

  89. Bartunek, J., et al. (2005). Intracoronary injection of CD133-positive enriched bone marrow progenitor cells promotes cardiac recovery after recent myocardial infarction: Feasibility and safety. Circulation, 112(9 Suppl), I178–I183.

    PubMed  Google Scholar 

  90. Erbs, S., et al. (2005). Transplantation of blood-derived progenitor cells after recanalization of chronic coronary artery occlusion: First randomized and placebo-controlled study. Circulation Research, 97(8), 756–762.

    PubMed  CAS  Google Scholar 

  91. Chen, S. L., et al. (2004). Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. American Journal of Cardiology, 94(1), 92–95.

    PubMed  Google Scholar 

  92. Boyle, A. J., et al. (2006). Intra-coronary high-dose CD34+ stem cells in patients with chronic ischemic heart disease: A 12-month follow-up. International Journal of Cardiology, 109(1), 21–27.

    PubMed  Google Scholar 

  93. Fuchs, S., et al. (2003). Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease: A feasibility study. Journal of the American College of Cardiology, 41(10), 1721–1724.

    PubMed  Google Scholar 

  94. Losordo, D. W., et al. (2007). Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: A phase I/IIa double-blind, randomized controlled trial. Circulation, 115(25), 3165–3172.

    PubMed  Google Scholar 

  95. Tse, H. F., et al. (2003). Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet, 361(9351), 47–49.

    PubMed  Google Scholar 

  96. Archundia, A., et al. (2005). Direct cardiac injection of G-CSF mobilized bone-marrow stem-cells improves ventricular function in old myocardial infarction. Life Science, 78(3), 279–283.

    CAS  Google Scholar 

  97. Assmus, B., et al. (2006). Transcoronary transplantation of progenitor cells after myocardial infarction. New England Journal of Medicine, 355(12), 1222–1232.

    PubMed  CAS  Google Scholar 

  98. Blatt, A., et al. (2005). Intracoronary administration of autologous bone marrow mononuclear cells after induction of short ischemia is safe and may improve hibernation and ischemia in patients with ischemic cardiomyopathy. American Heart Journal, 150(5), 986.

    PubMed  Google Scholar 

  99. de la Fuente, L. M., et al. (2007). Transendocardial autologous bone marrow in chronic myocardial infarction using a helical needle catheter: 1-year follow-up in an open-label, nonrandomized, single-center pilot study (the TABMMI study). American Heart Journal, 154(1), 79 e1–e7.

    Google Scholar 

  100. Hamano, K., et al. (2001). Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease: Clinical trial and preliminary results. Japanese Circulation Journal, 65(9), 845–847.

    PubMed  CAS  Google Scholar 

  101. Hendrikx, M., et al. (2006). Recovery of regional but not global contractile function by the direct intramyocardial autologous bone marrow transplantation: Results from a randomized controlled clinical trial. Circulation, 114(1 Suppl), I101–I107.

    PubMed  Google Scholar 

  102. Kuethe, F., et al. (2005). Autologous intracoronary mononuclear bone marrow cell transplantation in chronic ischemic cardiomyopathy in humans. International Journal of Cardiology, 100(3), 485–491.

    PubMed  Google Scholar 

  103. Manginas, A., et al. (2007). Pilot study to evaluate the safety and feasibility of intracoronary CD133(+) and CD133(−) CD34(+) cell therapy in patients with nonviable anterior myocardial infarction. Catheterization and Cardiovascular Interventions, 69(6), 773–781.

    PubMed  Google Scholar 

  104. Ozbaran, M., et al. (2004). Autologous peripheral stem cell transplantation in patients with congestive heart failure due to ischemic heart disease. European Journal of Cardio-thoracic Surgery, 25(3), 342–350 discussion 350–351.

    PubMed  Google Scholar 

  105. Patel, A. N., et al. (2005). Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: A prospective randomized study. Journal of Thoracic and Cardiovascular Surgery, 130(6), 1631–1638.

    PubMed  Google Scholar 

  106. Perin, E. C., et al. (2004). Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation, 110(11 Suppl 1), II213–II218.

    PubMed  Google Scholar 

  107. Silva, G. V., et al. (2004). Catheter-based transendocardial delivery of autologous bone-marrow-derived mononuclear cells in patients listed for heart transplantation. Texas Heart Institute Journal, 31(3), 214–219.

    PubMed  Google Scholar 

  108. Yaoita, H., et al. (2005). Scintigraphic assessment of the effects of bone marrow-derived mononuclear cell transplantation combined with off-pump coronary artery bypass surgery in patients with ischemic heart disease. Journal of Nuclear Med, 46(10), 1610–1617.

    Google Scholar 

  109. Perin, E. (2004). Transendocardial injection of autologous mononuclear bone marrow cells in end-stage ischemic heart failure patients: One-year follow-up. International Journal of Cardiology, 95(Suppl 1), S45–S46.

    PubMed  Google Scholar 

  110. Dawn, B., et al. (2005). Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. Proceedings of the National Academy of Sciences of the United States of America, 102(10), 3766–3771.

    PubMed  CAS  Google Scholar 

  111. Smith, R. R., et al. (2007). Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation, 115(7), 896–908.

    PubMed  CAS  Google Scholar 

  112. Moretti, A., et al. (2006). Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell, 127(6), 1151–1165.

    PubMed  CAS  Google Scholar 

  113. Menasche, P., et al. (2003). Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. Journal of the American College of Cardiology, 41(7), 1078–1083.

    PubMed  Google Scholar 

  114. Pagani, F. D., et al. (2003). Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans. Histological analysis of cell survival and differentiation. Journal of the American College of Cardiology, 41(5), 879–888.

    PubMed  Google Scholar 

  115. Herreros, J., et al. (2003). Autologous intramyocardial injection of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction. European Heart Journal, 24(22), 2012–2020.

    PubMed  Google Scholar 

  116. Smits, P. C., et al. (2003). Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: Clinical experience with six-month follow-up. Journal of the American College of Cardiology, 42(12), 2063–2069.

    PubMed  Google Scholar 

  117. Ince, H., et al. (2005). [Percutaneous transplantation of autologous myoblasts in ischemic cardiomyopathy]. Herz, 30(3), 223–231.

    PubMed  Google Scholar 

  118. Siminiak, T., et al. (2005). Percutaneous trans-coronary-venous transplantation of autologous skeletal myoblasts in the treatment of post-infarction myocardial contractility impairment: The POZNAN trial. European Heart Journal, 26(12), 1188–1195.

    PubMed  Google Scholar 

  119. Dib, N., et al. (2005). Feasibility and safety of autologous myoblast transplantation in patients with ischemic cardiomyopathy. Cell Transplantation, 14(1), 11–19.

    PubMed  Google Scholar 

  120. Dib, N., et al. (2005). Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: Four-year follow-up. Circulation, 112(12), 1748–1755.

    PubMed  Google Scholar 

  121. Kuethe, F., et al. (2004). Lack of regeneration of myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans with large anterior myocardial infarctions. International Journal Cardiology, 97(1), 123–127.

    Google Scholar 

  122. Fernandez-Aviles, F., et al. (2004). Experimental and clinical regenerative capability of human bone marrow cells after myocardial infarction. Circulation Reserach, 95(7), 742–748.

    CAS  Google Scholar 

  123. Strauer, B. E., et al. (2005). Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: The IACT study. Journal of the American College of Cardiology, 46(9), 1651–1658.

    PubMed  Google Scholar 

  124. Katritsis, D. G., et al. (2005). Transcoronary transplantation of autologous mesenchymal stem cells and endothelial progenitors into infarcted human myocardium. Catheterization and Cardiovascular Interventions, 65(3), 321–329.

    PubMed  Google Scholar 

  125. Ge, J., et al. (2006). Efficacy of emergent transcatheter transplantation of stem cells for treatment of acute myocardial infarction (TCT-STAMI). Heart, 92(12), 1764–1767.

    PubMed  CAS  Google Scholar 

  126. Kang, H. J., et al. (2006). Differential effect of intracoronary infusion of mobilized peripheral blood stem cells by granulocyte colony-stimulating factor on left ventricular function and remodeling in patients with acute myocardial infarction versus old myocardial infarction: The MAGIC cell-3-DES randomized, controlled trial. Circulation, 114(1 Suppl), I145–I151.

    PubMed  Google Scholar 

  127. Li, Z. Q., et al. (2007). The clinical study of autologous peripheral blood stem cell transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI). International Journal of Cardiology, 115(1), 52–56.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Cindy M. Martin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martin, C.M. Review of Stem Cell-Based Therapy for the Treatment of Cardiovascular Disease. J. of Cardiovasc. Trans. Res. 1, 106–114 (2008). https://doi.org/10.1007/s12265-008-9020-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-008-9020-6

Keywords

Navigation