Stem Cell Reviews and Reports

, Volume 9, Issue 3, pp 326–338 | Cite as

Cardiac Stem Cells and their Roles in Myocardial Infarction

  • Jingying Hou
  • Lingyun Wang
  • Jieyu Jiang
  • Changqing Zhou
  • Tianzhu Guo
  • Shaoxin Zheng
  • Tong Wang
Article

Abstract

Myocardial infarction leads to loss of cardiomyocytes, scar formation, ventricular remodeling and eventually deterioration of heart function. Over the past decade, stem cell therapy has emerged as a novel strategy for patients with ischemic heart disease and its beneficial effects have been demonstrated by substantial preclinical and clinical studies. Efficacy of several types of stem cells in the therapy of cardiovascular diseases has already been evaluated. However, repair of injured myocardium through stem cell transplantation is restricted by critical safety issues and ethic concerns. Recently, the discovery of cardiac stem cells (CSCs) that reside in the heart itself brings new prospects for myocardial regeneration and reconstitution of cardiac tissues. CSCs are positive for various stem cell markers and have the potential of self-renewal and multilineage differentiation. They play a pivotal role in the maintenance of heart homeostasis and cardiac repair. Elucidation of their biological characteristics and functions they exert in myocardial infarction are very crucial to further investigations on them. This review will focus on the field of cardiac stem cells and discuss technical and practical issues that may involve in their clinical applications in myocardial infarction.

Keywords

Cardiac stem cells Myocardial infarction Cell therapy Myocardial regeneration Cardiac repair 

Abbreviations

CSCs

Cardiac stem cells

MI

Myocardial infarction

CPCs

Cardiac progenitor cells

ESCs

Embryonic stem cells

BMSCs

Bone marrow stem cells

iPSCs

Induced pluripotent stem cells

EPCs

Embryo progenitor cells

BMPCs

Bone marrow progenitors cells

SP

Side population

LV

Left ventricular

mCSCs

Myogenic CSCs

vCSCs

Vasculogenic CSCs

IGF-1

Insulin-like growth factor 1

HGF

Hepatocyte growth factor

SDF-1

Stromal cell-derived factor-1

VEGF

Vascular endothelial growth factor

TGF-β

Transforming growth factor beta

BMP

Bone morphogenetic protein

References

  1. 1.
    Lloyd-Jones, D., Adams, R. J., Brown, T. M., et al. (2010). Executive summary: heart disease and stroke statistics–2010 update: a report from the American Heart Association. Circulation, 121(7), 948–954.PubMedCrossRefGoogle Scholar
  2. 2.
    Jameel, M. N., & Zhang, J. (2009). Heart failure management: the present and the future. Antioxidants & Redox Signaling, 11(8), 1989–2010.CrossRefGoogle Scholar
  3. 3.
    Donndorf, P., Strauer, B. E., & Steinhoff, G. (2012). Update on cardiac stem cell therapy in heart failure. Current Opinion in Cardiology, 27(2), 154–160.PubMedCrossRefGoogle Scholar
  4. 4.
    Choi, S. H., Jung, S. Y., Kwon, S. M., & Baek, S. H. (2012). Perspectives on stem cell therapy for cardiac regeneration. Circulation Journal, 76(6), 1307–1312.PubMedCrossRefGoogle Scholar
  5. 5.
    Abdelwahid, E., Siminiak, T., Guarita-Souza, L. C., et al. (2011). Stem cell therapy in heart diseases: a review of selected new perspectives, practical considerations and clinical applications. Current Cardiology Reviews, 7(3), 201–212.PubMedCrossRefGoogle Scholar
  6. 6.
    Caspi, O., Huber, I., Kehat, I., et al. (2007). Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. Journal of the American College of Cardiology, 50(19), 1884–1893.PubMedCrossRefGoogle Scholar
  7. 7.
    Adler, D. S., Lazarus, H., Nair, R., et al. (2011). Safety and efficacy of bone marrow-derived autologous CD133+ stem cell therapy. Frontiers in Bioscience (Elite Edition), 3, 506–514.CrossRefGoogle Scholar
  8. 8.
    Wang, T., Tang, W., Sun, S., et al. (2009). Mesenchymal stem cells improve outcomes of cardiopulmonary resuscitation in myocardial infarcted rats. Journal of Molecular and Cellular Cardiology, 46(3), 378–384.PubMedCrossRefGoogle Scholar
  9. 9.
    Dai, B., Huang, W., Xu, M., et al. (2011). Reduced collagen deposition in infarcted myocardium facilitates induced pluripotent stem cell engraftment and angiomyogenesis for improvement of left ventricular function. Journal of the American College of Cardiology, 58(20), 2118–2127.PubMedCrossRefGoogle Scholar
  10. 10.
    Lodi, D., Iannitti, T., & Palmieri, B. (2011). Stem cells in clinical practice: applications and warnings. Journal of Experimental & Clinical Cancer Research, 30(1), 9.CrossRefGoogle Scholar
  11. 11.
    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(11), 1340–1347.PubMedCrossRefGoogle Scholar
  12. 12.
    Ahmed, R. P., Ashraf, M., Buccini, S., Shujia, J., & Haider, H. (2011). Cardiac tumorigenic potential of induced pluripotent stem cells in an immunocompetent host with myocardial infarction. Regenerative Medicine, 6(2), 171–178.PubMedCrossRefGoogle Scholar
  13. 13.
    Breitbach, M., Bostani, T., Roell, W., et al. (2007). Potential risks of bone marrow cell transplantation into infarcted hearts. Blood, 110(4), 1362–1369.PubMedCrossRefGoogle Scholar
  14. 14.
    Rubart, M., & Field, L. J. (2006). Cardiac regeneration: repopulating the heart. Annual Review of Physiology, 68, 29–49.PubMedCrossRefGoogle Scholar
  15. 15.
    Kajstura, J., Gurusamy, N., Ogorek, B., et al. (2010). Myocyte turnover in the aging human heart. Circulation Research, 107(11), 1374–1386.PubMedCrossRefGoogle Scholar
  16. 16.
    Bergmann, O., Bhardwaj, R. D., Bernard, S., et al. (2009). Evidence for cardiomyocyte renewal in humans. Science, 324(5923), 98–102.PubMedCrossRefGoogle Scholar
  17. 17.
    Bostrom, P., Mann, N., Wu, J., et al. (2010). C/EBPbeta controls exercise-induced cardiac growth and protects against pathological cardiac remodeling. Cell, 143(7), 1072–1083.PubMedCrossRefGoogle Scholar
  18. 18.
    Kajstura, J., Urbanek, K., Perl, S., et al. (2010). Cardiomyogenesis in the adult human heart. Circulation Research, 107(2), 305–315.PubMedCrossRefGoogle Scholar
  19. 19.
    Leri, A., Kajstura, J., & Anversa, P. (2011). Role of cardiac stem cells in cardiac pathophysiology: a paradigm shift in human myocardial biology. Circulation Research, 109(8), 941–961.PubMedCrossRefGoogle Scholar
  20. 20.
    Frati, C., Savi, M., Graiani, G., et al. (2011). Resident cardiac stem cells. Current Pharmaceutical Design, 17(30), 3252–3257.PubMedCrossRefGoogle Scholar
  21. 21.
    Hsieh, P. C., Segers, V. F., Davis, M. E., et al. (2007). Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury. Nature Medicine, 13(8), 970–974.PubMedCrossRefGoogle Scholar
  22. 22.
    Hosoda, T., Kajstura, J., Leri, A., & Anversa, P. (2010). Mechanisms of myocardial regeneration. Circulation Journal, 74(1), 13–17.PubMedCrossRefGoogle Scholar
  23. 23.
    Sussman, M. A., & Murry, C. E. (2008). Bones of contention: marrow-derived cells in myocardial regeneration. Journal of Molecular and Cellular Cardiology, 44(6), 950–953.PubMedCrossRefGoogle Scholar
  24. 24.
    Vincent, S. D., & Buckingham, M. E. (2010). How to make a heart: the origin and regulation of cardiac progenitor cells. Current Topics in Developmental Biology, 90, 1–41.PubMedCrossRefGoogle Scholar
  25. 25.
    Chimenti, I., Gaetani, R., Barile, L., et al. (2012). Isolation and expansion of adult cardiac stem/progenitor cells in the form of cardiospheres from human cardiac biopsies and murine hearts. Methods in Molecular Biology, 879, 327–338.PubMedCrossRefGoogle Scholar
  26. 26.
    Angelini, A., Castellani, C., Tona, F., et al. (2007). Continuous engraftment and differentiation of male recipient Y-chromosome-positive cardiomyocytes in donor female human heart transplants. The Journal of Heart and Lung Transplantation, 26(11), 1110–1118.PubMedCrossRefGoogle Scholar
  27. 27.
    Jiang, H., Tu, H., Chen, Z., et al. (2011). Effects of chimerism on the mice heart transplanted survival with the bone marrow infusion. Transplant Immunology, 25(4), 202–206.PubMedCrossRefGoogle Scholar
  28. 28.
    Wu, S. M., Fujiwara, Y., Cibulsky, S. M., et al. (2006). Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart. Cell, 127(6), 1137–1150.PubMedCrossRefGoogle Scholar
  29. 29.
    Serradifalco, C., Catanese, P., Rizzuto, L., et al. (2011). Embryonic and foetal Islet-1 positive cells in human hearts are also positive to c-Kit. European Journal of Histochemistry, 55(4), e41.PubMedCrossRefGoogle Scholar
  30. 30.
    Barile, L., Messina, E., Giacomello, A., & Marban, E. (2007). Endogenous cardiac stem cells. Progress in Cardiovascular Diseases, 50(1), 31–48.PubMedCrossRefGoogle Scholar
  31. 31.
    Davis, D. R., Kizana, E., Terrovitis, J., et al. (2010). Isolation and expansion of functionally-competent cardiac progenitor cells directly from heart biopsies. Journal of Molecular and Cellular Cardiology, 49(2), 312–321.PubMedCrossRefGoogle Scholar
  32. 32.
    D'Amario, D., Fiorini, C., Campbell, P. M., et al. (2011). Functionally competent cardiac stem cells can be isolated from endomyocardial biopsies of patients with advanced cardiomyopathies. Circulation Research, 108(7), 857–861.PubMedCrossRefGoogle Scholar
  33. 33.
    Beltrami, A. P., Barlucchi, L., Torella, D., et al. (2003). Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell, 114(6), 763–776.PubMedCrossRefGoogle Scholar
  34. 34.
    Ferreira-Martins, J., Ogorek, B., Cappetta, D., et al. (2012). Cardiomyogenesis in the developing heart is regulated by c-kit-positive cardiac stem cells. Circulation Research, 110(5), 701–715.PubMedCrossRefGoogle Scholar
  35. 35.
    He, J. Q., Vu, D. M., Hunt, G., Chugh, A., Bhatnagar, A., & Bolli, R. (2011). Human cardiac stem cells isolated from atrial appendages stably express c-kit. PLoS One, 6(11), e27719.PubMedCrossRefGoogle Scholar
  36. 36.
    Zaruba, M. M., Soonpaa, M., Reuter, S., & Field, L. J. (2010). Cardiomyogenic potential of C-kit(+)-expressing cells derived from neonatal and adult mouse hearts. Circulation, 121(18), 1992–2000.PubMedCrossRefGoogle Scholar
  37. 37.
    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(7), 913–922.PubMedCrossRefGoogle Scholar
  38. 38.
    Craven, M., Kotlikoff, M. I., & Nadworny, A. S. (2012). C-kit expression identifies cardiac precursor cells in neonatal mice. Methods in Molecular Biology, 843, 177–189.PubMedCrossRefGoogle Scholar
  39. 39.
    Li, Q., Guo, Y., Ou, Q., et al. (2011). Intracoronary administration of cardiac stem cells in mice: a new, improved technique for cell therapy in murine models. Basic Research in Cardiology, 106(5), 849–864.PubMedCrossRefGoogle Scholar
  40. 40.
    Oh, H., Bradfute, S. B., Gallardo, T. D., et al. (2003). Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proceedings of the National Academy of Sciences of the United States of America, 100(21), 12313–123138.PubMedCrossRefGoogle Scholar
  41. 41.
    Matsuura, K., Nagai, T., Nishigaki, N., et al. (2004). Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. The Journal of Biological Chemistry, 279(12), 11384–11391.PubMedCrossRefGoogle Scholar
  42. 42.
    van Vliet, P., Roccio, M., Smits, A. M., et al. (2008). Progenitor cells isolated from the human heart: a potential cell source for regenerative therapy. Netherlands Heart Journal, 16(5), 163–169.PubMedCrossRefGoogle Scholar
  43. 43.
    Wang, X., Hu, Q., Nakamura, Y., et al. (2006). The role of the sca-1+/CD31- cardiac progenitor cell population in postinfarction left ventricular remodeling. Stem Cells, 24(7), 1779–1788.PubMedCrossRefGoogle Scholar
  44. 44.
    Goumans, M. J., de Boer, T. P., Smits, A. M., et al. (2007). TGF-beta1 induces efficient differentiation of human cardiomyocyte progenitor cells into functional cardiomyocytes in vitro. Stem Cell Research, 1(2), 138–149.PubMedCrossRefGoogle Scholar
  45. 45.
    Matsuura, K., Honda, A., Nagai, T., et al. (2009). Transplantation of cardiac progenitor cells ameliorates cardiac dysfunction after myocardial infarction in mice. The Journal of Clinical Investigation, 119(8), 2204–2217.PubMedGoogle Scholar
  46. 46.
    Samal, R., Ameling, S., Wenzel, K., et al. (2012). OMICS-based exploration of the molecular phenotype of resident cardiac progenitor cells from adult murine heart. Journal of Proteomics, [Epub ahead of print] Jun 27.Google Scholar
  47. 47.
    Shi, C., Li, Q., Zhao, Y., et al. (2011). Stem-cell-capturing collagen scaffold promotes cardiac tissue regeneration. Biomaterials, 32(10), 2508–2515.PubMedCrossRefGoogle Scholar
  48. 48.
    Hierlihy, A. M., Seale, P., Lobe, C. G., Rudnicki, M. A., & Megeney, L. A. (2002). The post-natal heart contains a myocardial stem cell population. FEBS Letters, 530(1–3), 239–243.PubMedCrossRefGoogle Scholar
  49. 49.
    Pfister, O., Oikonomopoulos, A., Sereti, K. I., et al. (2008). Role of the ATP-binding cassette transporter Abcg2 in the phenotype and function of cardiac side population cells. Circulation Research, 103(8), 825–835.PubMedCrossRefGoogle Scholar
  50. 50.
    Unno, K., Jain, M., & Liao, R. (2012). Cardiac side population cells: moving toward the center stage in cardiac regeneration. Circulation Research, 110(10), 1355–1363.PubMedCrossRefGoogle Scholar
  51. 51.
    Oyama, T., Nagai, T., Wada, H., et al. (2007). Cardiac side population cells have a potential to migrate and differentiate into cardiomyocytes in vitro and in vivo. The Journal of Cell Biology, 176(3), 329–341.PubMedCrossRefGoogle Scholar
  52. 52.
    Liang, S. X., Tan, T. Y., Gaudry, L., & Chong, B. (2010). Differentiation and migration of Sca1+/CD31- cardiac side population cells in a murine myocardial ischemic model. International Journal of Cardiology, 138(1), 40–49.PubMedCrossRefGoogle Scholar
  53. 53.
    Wohlschlaeger, J., Levkau, B., Takeda, A., et al. (2012). Increase of ABCG2/BCRP+ side population stem cells in myocardium after ventricular unloading. The Journal of Heart and Lung Transplantation, 31(3), 318–324.PubMedCrossRefGoogle Scholar
  54. 54.
    Messina, E., De Angelis, L., Frati, G., et al. (2004). Isolation and expansion of adult cardiac stem cells from human and murine heart. Circulation Research, 95(9), 911–921.PubMedCrossRefGoogle Scholar
  55. 55.
    Li, T. S., Cheng, K., Malliaras, K., et al. (2012). Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells. Journal of the American College of Cardiology, 59(10), 942–953.PubMedCrossRefGoogle Scholar
  56. 56.
    Ye, J., Boyle, A., Shih, H., et al. (2012). Sca-1+ cardiosphere-derived cells are enriched for Isl1-expressing cardiac precursors and improve cardiac function after myocardial injury. PLoS One, 7(1), e30329.PubMedCrossRefGoogle Scholar
  57. 57.
    Smith, R. R., Barile, L., Cho, H. C., et al. (2007). Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation, 115(7), 896–908.PubMedCrossRefGoogle Scholar
  58. 58.
    Li, T. S., Cheng, K., Lee, S. T., et al. (2010). Cardiospheres recapitulate a niche-like microenvironment rich in stemness and cell-matrix interactions, rationalizing their enhanced functional potency for myocardial repair. Stem Cells, 28(11), 2088–2098.PubMedCrossRefGoogle Scholar
  59. 59.
    Johnston, P. V., Sasano, T., Mills, K., et al. (2009). Engraftment, differentiation, and functional benefits of autologous cardiosphere-derived cells in porcine ischemic cardiomyopathy. Circulation, 120(12), 1075–1083. 7-1083.PubMedCrossRefGoogle Scholar
  60. 60.
    Moretti, A., Lam, J., Evans, S. M., & Laugwitz, K. L. (2007). Biology of Isl1+ cardiac progenitor cells in development and disease. Cellular and Molecular Life Sciences, 64(6), 674–682.PubMedCrossRefGoogle Scholar
  61. 61.
    Bu, L., Jiang, X., Martin-Puig, S., et al. (2009). Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages. Nature, 460(7251), 113–117.PubMedCrossRefGoogle Scholar
  62. 62.
    Pandur, P., Sirbu, I. O., Kuhl, S. J., Philipp, M., & Kuhl, M. (2012). Islet1-expressing cardiac progenitor cells: a comparison across species. Development Genes and Evolution, [Epub ahead of print] Apr 24.Google Scholar
  63. 63.
    Genead, R., Danielsson, C., Andersson, A. B., et al. (2010). Islet-1 cells are cardiac progenitors present during the entire lifespan: from the embryonic stage to adulthood. Stem Cells and Development, 19(10), 1601–1615.PubMedCrossRefGoogle Scholar
  64. 64.
    Moretti, A., Caron, L., Nakano, A., et al. (2006). Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell, 127(6), 1151–1165.PubMedCrossRefGoogle Scholar
  65. 65.
    Barzelay, A., Ben-Shoshan, J., Entin-Meer, M., et al. (2010). A potential role for islet-1 in post-natal angiogenesis and vasculogenesis. Thrombosis and Haemostasis, 103(1), 188–197.PubMedCrossRefGoogle Scholar
  66. 66.
    Huang, C. Q., Kim, L., Gude, N., et al. (2008). Juvenile anthracycline treatment contributes to heart failure in adulthood by impairing vascularization and cardiac stem cell function. Circulation Research, 103(5), 66.Google Scholar
  67. 67.
    Hosoda, T. (2012). C-kit-positive cardiac stem cells and myocardial regeneration. American Journal of Cardiovascular Diseases, 2(1), 58–67.Google Scholar
  68. 68.
    Takamiya, M., Haider, K. H., & Ashraf, M. (2011). Identification and characterization of a novel multipotent sub-population of Sca-1(+) cardiac progenitor cells for myocardial regeneration. PLoS One, 6(9), e25265.PubMedCrossRefGoogle Scholar
  69. 69.
    Borillo, G. A., Mason, M., Quijada, P., et al. (2010). Pim-1 kinase protects mitochondrial integrity in cardiomyocytes. Circulation Research, 106(7), 1265–1274.PubMedCrossRefGoogle Scholar
  70. 70.
    Cottage, C. T., Bailey, B., Fischer, K. M., et al. (2010). Cardiac progenitor cell cycling stimulated by pim-1 kinase. Circulation Research, 106(5), 891–901.PubMedCrossRefGoogle Scholar
  71. 71.
    Sundararaman, B., Avitabile, D., Konstandin, M. H., Cottage, C. T., Gude, N., & Sussman, M. A. (2012). Asymmetric chromatid segregation in cardiac progenitor cells is enhanced by Pim-1 kinase. Circulation Research, 110(9), 1169–1173.PubMedCrossRefGoogle Scholar
  72. 72.
    Hosoda, T., D'Amario, D., Cabral-Da-Silva, M. C., et al. (2009). Clonality of mouse and human cardiomyogenesis in vivo. Proceedings of the National Academy of Sciences of the United States of America, 106(40), 17169–17174.PubMedCrossRefGoogle Scholar
  73. 73.
    Ferreira-Martins, J., Rondon-Clavo, C., Tugal, D., et al. (2009). Spontaneous calcium oscillations regulate human cardiac progenitor cell growth. Circulation Research, 105(8), 764–774.PubMedCrossRefGoogle Scholar
  74. 74.
    Bailey, B., Izarra, A., Alvarez, R., et al. (2009). Cardiac stem cell genetic engineering using the alphaMHC promoter. Regenerative Medicine, 4(6), 823–833.PubMedCrossRefGoogle Scholar
  75. 75.
    Bearzi, C., Rota, M., Hosoda, T., et al. (2007). Human cardiac stem cells. Proceedings of the National Academy of Sciences of the United States of America, 104(35), 14068–14073.PubMedCrossRefGoogle Scholar
  76. 76.
    Bearzi, C., Leri, A., Lo, M. F., et al. (2009). Identification of a coronary vascular progenitor cell in the human heart. Proceedings of the National Academy of Sciences of the United States of America, 106(37), 15885–15890.PubMedCrossRefGoogle Scholar
  77. 77.
    Barrilleaux, B., & Knoepfler, P. S. (2011). Inducing iPSCs to escape the dish. Cell Stem Cell, 9(2), 103–111.PubMedCrossRefGoogle Scholar
  78. 78.
    Mohri, T., Fujio, Y., Maeda, M., et al. (2006). Leukemia inhibitory factor induces endothelial differentiation in cardiac stem cells. The Journal of Biological Chemistry, 281(10), 6442–6447.PubMedCrossRefGoogle Scholar
  79. 79.
    Iwakura, T., Mohri, T., Hamatani, T., et al. (2011). STAT3/Pim-1 signaling pathway plays a crucial role in endothelial differentiation of cardiac resident Sca-1+ cells both in vitro and in vivo. Journal of Molecular and Cellular Cardiology, 51(12), 207–214.PubMedCrossRefGoogle Scholar
  80. 80.
    Mohri, T., Fujio, Y., Obana, M., et al. (2009). Signals through glycoprotein 130 regulate the endothelial differentiation of cardiac stem cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 29(5), 754–760.PubMedCrossRefGoogle Scholar
  81. 81.
    Zakharova, L., Mastroeni, D., Mutlu, N., et al. (2010). Transplantation of cardiac progenitor cell sheet onto infarcted heart promotes cardiogenesis and improves function. Cardiovascular Research, 87(1), 40–49.PubMedCrossRefGoogle Scholar
  82. 82.
    Suzuki, R., Li, T. S., Mikamo, A., et al. (2007). The reduction of hemodynamic loading assists self-regeneration of the injured heart by increasing cell proliferation, inhibiting cell apoptosis, and inducing stem-cell recruitment. The Journal of Thoracic and Cardiovascular Surgery, 133(4), 1051–1058.PubMedCrossRefGoogle Scholar
  83. 83.
    Wen, Z., Zheng, S., Zhou, C., Wang, J., & Wang, T. (2011). Repair mechanisms of bone marrow mesenchymal stem cells in myocardial infarction. Journal of Cellular and Molecular Medicine, 15(5), 1032–1043.PubMedCrossRefGoogle Scholar
  84. 84.
    Wen, Z., Zheng, S., Zhou, C., Yuan, W., Wang, J., & Wang, T. (2012). Bone marrow mesenchymal stem cells for post-myocardial infarction cardiac repair: microRNAs as novel regulators. Journal of Cellular and Molecular Medicine, 16(4), 657–671.PubMedCrossRefGoogle Scholar
  85. 85.
    Ratajczak, M. Z., Kucia, M., Jadczyk, T., et al. (2012). Pivotal role of paracrine effects in stem cell therapies in regenerative medicine: can we translate stem cell-secreted paracrine factors and microvesicles into better therapeutic strategies? Leukemia, 26(6), 1166–1173.PubMedCrossRefGoogle Scholar
  86. 86.
    Gnecchi, M., Zhang, Z., Ni, A., & Dzau, V. J. (2008). Paracrine mechanisms in adult stem cell signaling and therapy. Circulation Research, 103(11), 1204–1219.PubMedCrossRefGoogle Scholar
  87. 87.
    Chimenti, I., Smith, R. R., Li, T. S., et al. (2010). Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infarcted mice. Circulation Research, 106(5), 971–980.PubMedCrossRefGoogle Scholar
  88. 88.
    Miyamoto, S., Kawaguchi, N., Ellison, G. M., Matsuoka, R., Shin'oka, T., & Kurosawa, H. (2010). Characterization of long-term cultured c-kit+ cardiac stem cells derived from adult rat hearts. Stem Cells and Development, 19(1), 105–116.PubMedCrossRefGoogle Scholar
  89. 89.
    D'Amario, D., Cabral-Da-Silva, M. C., Zheng, H., et al. (2011). Insulin-like growth factor-1 receptor identifies a pool of human cardiac stem cells with superior therapeutic potential for myocardial regeneration. Circulation Research, 108(12), 1467–1481.PubMedCrossRefGoogle Scholar
  90. 90.
    Padin-Iruegas, M. E., Misao, Y., Davis, M. E., et al. (2009). Cardiac progenitor cells and biotinylated insulin-like growth factor-1 nanofibers improve endogenous and exogenous myocardial regeneration after infarction. Circulation, 120(10), 876–887.PubMedCrossRefGoogle Scholar
  91. 91.
    Lu, G., Haider, H. K., Jiang, S., & Ashraf, M. (2009). Sca-1+ stem cell survival and engraftment in the infarcted heart: dual role for preconditioning-induced connexin-43. Circulation, 119(19), 2587–2596.PubMedCrossRefGoogle Scholar
  92. 92.
    Urbanek, K., Rota, M., Cascapera, S., et al. (2005). Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circulation Research, 97(7), 663–673.PubMedCrossRefGoogle Scholar
  93. 93.
    Rota, M., Padin-Iruegas, M. E., Misao, Y., et al. (2008). Local activation or implantation of cardiac progenitor cells rescues scarred infarcted myocardium improving cardiac function. Circulation Research, 103(1), 107–116.PubMedCrossRefGoogle Scholar
  94. 94.
    Linke, A., Muller, P., Nurzynska, D., et al. (2005). Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. Proceedings of the National Academy of Sciences of the United States of America, 102(25), 8966–8971.PubMedCrossRefGoogle Scholar
  95. 95.
    Gonzalez, A., Rota, M., Nurzynska, D., et al. (2008). Activation of cardiac progenitor cells reverses the failing heart senescent phenotype and prolongs lifespan. Circulation Research, 102(5), 597–606.PubMedCrossRefGoogle Scholar
  96. 96.
    Kuijper, S., Turner, C. J., & Adams, R. H. (2007). Regulation of angiogenesis by Eph-ephrin interactions. Trends in Cardiovascular Medicine, 17(5), 145–151.PubMedCrossRefGoogle Scholar
  97. 97.
    Pasquale, E. B. (2008). Eph-ephrin bidirectional signaling in physiology and disease. Cell, 133(1), 38–52.PubMedCrossRefGoogle Scholar
  98. 98.
    Goichberg, P., Bai, Y., D'Amario, D., et al. (2011). The ephrin A1-EphA2 system promotes cardiac stem cell migration after infarction. Circulation Research, 108(9), 1071–1083.PubMedCrossRefGoogle Scholar
  99. 99.
    Ellison, G. M., Torella, D., Dellegrottaglie, S., 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(9), 977–986.PubMedCrossRefGoogle Scholar
  100. 100.
    Hu, X., Dai, S., Wu, W. J., et al. (2007). Stromal cell derived factor-1 alpha confers protection against myocardial ischemia/reperfusion injury: role of the cardiac stromal cell derived factor-1 alpha CXCR4 axis. Circulation, 116(6), 654–663.PubMedCrossRefGoogle Scholar
  101. 101.
    Huang, C., Gu, H., Yu, Q., Manukyan, M. C., Poynter, J. A., & Wang, M. (2011). Sca-1+ cardiac stem cells mediate acute cardioprotection via paracrine factor SDF-1 following myocardial ischemia/reperfusion. PLoS One, 6(12), e29246.PubMedCrossRefGoogle Scholar
  102. 102.
    Tang, J. M., Wang, J. N., Zhang, L., et al. (2011). VEGF/SDF-1 promotes cardiac stem cell mobilization and myocardial repair in the infarcted heart. Cardiovascular Research, 91(3), 402–411.PubMedCrossRefGoogle Scholar
  103. 103.
    Yu, J., Li, M., Qu, Z., Yan, D., Li, D., & Ruan, Q. (2010). SDF-1/CXCR4-mediated migration of transplanted bone marrow stromal cells toward areas of heart myocardial infarction through activation of PI3K/Akt. Journal of Cardiovascular Pharmacology, 55(5), 496–505.PubMedGoogle Scholar
  104. 104.
    Kawaguchi, N., Nakao, R., Yamaguchi, M., Ogawa, D., & Matsuoka, R. (2010). TGF-beta superfamily regulates a switch that mediates differentiation either into adipocytes or myocytes in left atrium derived pluripotent cells (LA-PCS). Biochemical and Biophysical Research Communications, 396(3), 619–625.PubMedCrossRefGoogle Scholar
  105. 105.
    Kawaguchi, N. (2011). Adult cardiac-derived stem cells: differentiation and survival regulators. Vitamins and Hormones, 87, 111–125.PubMedCrossRefGoogle Scholar
  106. 106.
    Martin, L. K., Mezentseva, N. V., Bratoeva, M., Ramsdell, A. F., Eisenberg, C. A., & Eisenberg, L. M. (2011). Canonical WNT signaling enhances stem cell expression in the developing heart without a corresponding inhibition of cardiogenic differentiation. Stem Cells and Development, 20(11), 1973–1983.PubMedCrossRefGoogle Scholar
  107. 107.
    Klaus, A., Muller, M., Schulz, H., Saga, Y., Martin, J. F., & Birchmeier, W. (2012). Wnt/beta-catenin and Bmp signals control distinct sets of transcription factors in cardiac progenitor cells. Proceedings of the National Academy of Sciences of the United States of America, 109(27), 10921–10926.PubMedCrossRefGoogle Scholar
  108. 108.
    Boni, A., Urbanek, K., Nascimbene, A., et al. (2008). Notch1 regulates the fate of cardiac progenitor cells. Proceedings of the National Academy of Sciences of the United States of America, 105(40), 15529–15534.PubMedCrossRefGoogle Scholar
  109. 109.
    Mishra, P. K., Chavali, V., Metreveli, N., & Tyagi, S. C. (2012). Ablation of MMP9 induces survival and differentiation of cardiac stem cells into cardiomyocytes in the heart of diabetics: a role of extracellular matrix. Canadian Journal of Physiology and Pharmacology, 90(3), 353–360.PubMedCrossRefGoogle Scholar
  110. 110.
    Zhang, X., Zhang, C. S., Liu, Y. C., et al. (2009). Isolation, culture and characterization of cardiac progenitor cells derived from human embryonic heart tubes. Cells, Tissues, Organs, 190(4), 194–208.PubMedCrossRefGoogle Scholar
  111. 111.
    Ortiz-Perez, J. T., Lee, D. C., Meyers, S. N., Davidson, C. J., Bonow, R. O., & Wu, E. (2010). Determinants of myocardial salvage during acute myocardial infarction: evaluation with a combined angiographic and CMR myocardial salvage index. JACC. Cardiovascular Imaging, 3(5), 491–500.PubMedCrossRefGoogle Scholar
  112. 112.
    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(4), 455–465.PubMedCrossRefGoogle Scholar
  113. 113.
    Zheng, S., Zhou, C., Weng, Y., et al. (2011). Improvements of cardiac electrophysiologic stability and ventricular fibrillation threshold in rats with myocardial infarction treated with cardiac stem cells. Critical Care Medicine, 39(5), 1082–1088.PubMedCrossRefGoogle Scholar
  114. 114.
    de Boer, T. P., van Veen, T. A., Jonsson, M. K., et al. (2010). Human cardiomyocyte progenitor cell-derived cardiomyocytes display a maturated electrical phenotype. Journal of Molecular and Cellular Cardiology, 48(1), 254–260.PubMedCrossRefGoogle Scholar
  115. 115.
    Takehara, N., Tsutsumi, Y., Tateishi, K., et al. (2008). Controlled delivery of basic fibroblast growth factor promotes human cardiosphere-derived cell engraftment to enhance cardiac repair for chronic myocardial infarction. Journal of the American College of Cardiology, 52(23), 1858–1865.PubMedCrossRefGoogle Scholar
  116. 116.
    Makkar, R. R., Smith, R. R., Cheng, K., et al. (2012). Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet, 379(9819), 895–904.PubMedCrossRefGoogle Scholar
  117. 117.
    Bolli, R., Chugh, A. R., D'Amario, D., et al. (2011). Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet, 378(9806), 1847–1857.PubMedCrossRefGoogle Scholar
  118. 118.
    Bollini, S., Smart, N., & Riley, P. R. (2011). Resident cardiac progenitor cells: at the heart of regeneration. Journal of Molecular and Cellular Cardiology, 50(2), 296–303.PubMedCrossRefGoogle Scholar
  119. 119.
    Dib, N., Menasche, P., Bartunek, J. J., et al. (2010). Recommendations for successful training on methods of delivery of biologics for cardiac regeneration: a report of the International Society for Cardiovascular Translational Research. JACC. Cardiovascular Interventions, 3(3), 265–275.PubMedCrossRefGoogle Scholar
  120. 120.
    Ye, Z., Zhou, Y., Cai, H., & Tan, W. (2011). Myocardial regeneration: roles of stem cells and hydrogels. Advanced Drug Delivery Reviews, 63(8), 688–697.PubMedCrossRefGoogle Scholar
  121. 121.
    Freed, L. E., Jr., Engelmayr, G. C., Borenstein, J. T., Moutos, F. T., & Guilak, F. (2009). Advanced material strategies for tissue engineering scaffolds. Advanced Materials, 21(12), 3410–3418.PubMedCrossRefGoogle Scholar
  122. 122.
    Li, T. S., Cheng, K., Malliaras, K., et al. (2011). Expansion of human cardiac stem cells in physiological oxygen improves cell production efficiency and potency for myocardial repair. Cardiovascular Research, 89(1), 157–165.PubMedCrossRefGoogle Scholar
  123. 123.
    Kurazumi, H., Kubo, M., Ohshima, M., et al. (2011). The effects of mechanical stress on the growth, differentiation, and paracrine factor production of cardiac stem cells. PLoS One, 6(12), e28890.PubMedCrossRefGoogle Scholar
  124. 124.
    Gao, H., Priebe, W., Glod, J., & Banerjee, D. (2009). Activation of signal transducers and activators of transcription 3 and focal adhesion kinase by stromal cell-derived factor 1 is required for migration of human mesenchymal stem cells in response to tumor cell-conditioned medium. Stem Cells, 27(4), 857–865.PubMedCrossRefGoogle Scholar
  125. 125.
    Saxena, A., Fish, J. E., White, M. D., et al. (2008). Stromal cell-derived factor-1alpha is cardioprotective after myocardial infarction. Circulation, 117(17), 2224–2231.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Jingying Hou
    • 1
  • Lingyun Wang
    • 2
  • Jieyu Jiang
    • 1
  • Changqing Zhou
    • 1
  • Tianzhu Guo
    • 1
  • Shaoxin Zheng
    • 3
  • Tong Wang
    • 1
    • 4
  1. 1.Department of EmergencyThe Sun Yat-sen Memorial Hospital of Sun Yat-sen UniversityGuangzhouChina
  2. 2.Department of GastroenterologyThe Sun Yat-sen Memorial Hospital of Sun Yat-sen UniversityGuangzhouChina
  3. 3.Department of CardiologyThe Sun Yat-sen Memorial Hospital of Sun Yat-sen UniversityGuangzhouChina
  4. 4.Center for Stem Cell Biology and Tissue Engineering, Ministry of EducationSun Yat-sen UniversityGuangzhouChina

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