Cardiovascular Toxicology

, Volume 8, Issue 1, pp 1–13

Adhesion Proteins, Stem Cells, and Arrhythmogenesis

Article

Abstract

Cell-transplantation therapy is a promising treatment option that is being actively explored as a way to repair cardiac muscle. The ultimate goal is to reconstitute the architecture of the cardiac muscle and to reestablish electrical propagation, while avoiding hypertrophy and scar formation. In this review, we focus on recent advances in the field as well as the difficulties encountered when the engraftment of cells into the host tissue is to be confirmed and functionally characterized. This is critical since incomplete or partial engraftment of transplanted cells within the host cardiac network exacerbates the heterogeneity already present in the injured myocardium and increases its propensity to arrhythmia. We conclude with a brief discussion of how the modulation of cell adhesion via modification of coupling proteins within transplanted cells may facilitate engraftment and alleviate the arrhythmogenic potential of cardiac grafts.

Keywords

Adhesion proteins Stem cells Arrhythmogenesis N-cadherin Intercalated disc 

References

  1. 1.
    Beltrami, A. P., Urbanek, K., Kajstura, J., Yan, S. M., Finato, N., Bussani, R., Nadal-Ginard, B., Silvestri, F., Leri, A., Beltrami, C. A., & Anversa, P. (2001). Evidence that human cardiac myocytes divide after myocardial infarction. New England Journal of Medicine, 344, 1750–1757.PubMedGoogle Scholar
  2. 2.
    Yuasa, S., Fukuda, K., Tomita, Y., Fujita, J., Ieda, M., Tahara, S., Itabashi, Y., Yagi, T., Kawaguchi, H., Hisaka, Y., & Ogawa, S. (2004). Cardiomyocytes undergo cells division following myocardial infarction is a spatially and temporally restricted event in rats. Molecular and Cellular Biochemistry, 259, 177–181.PubMedGoogle Scholar
  3. 3.
    Gaudesius, G., Miragoli, M., Thomas, S. P., & Rohr, S. (2003). Coupling of cardiac electrical activity over extended distances by fibroblasts of cardiac origin. Circulation Research, 93, 421–428.PubMedGoogle Scholar
  4. 4.
    Breithardt, G., Borggrefe, M., Martinez-Rubio, A., & Budde, T. (1989). Pathophysiological mechanisms of ventricular tachyarrhythmias. European Heart Journal, 10(Suppl E), 9–18.PubMedGoogle Scholar
  5. 5.
    Assayag, P., Carre, F., Chevalier, B., Delcayre, C., Mansier, P., & Swynghedauw, B. (1997). Compensated cardiac hypertrophy: Arrhythmogenicity and the new myocardial phenotype I. Fibrosis. Cardiovascular Research, 34, 439–444.PubMedGoogle Scholar
  6. 6.
    Rosamond, W., Flegal, K., Friday, G., Furie, K., Go, A., Greenlund, K., Haase, N., Ho, M., Howard, V., Kissela, B., Kittner, S., Lloyd-Jones, D., McDermott, M., Meigs, J., Moy, C., Nichol, G., O’Donnell, C. J., Roger, V., Rumsfeld, J., Sorlie, P., Steinberger, J., Thom, T., Wasserthiel-Smoller, S., & Hong, Y. (2007). Heart disease and stroke statistics-2007 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation, 115, e69–171.PubMedGoogle Scholar
  7. 7.
    Laugwitz, K. L., Moretti, A., Lam, J., Gruber, P., Chen, Y., Woodard, S., Lin, L. Z., Cai, C. L., Lu, M. M., Reth, M., Platoshyn, O., Yuan, J. X., Evans, S., & Chien, K. R. (2005). Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature, 433, 647–653.PubMedGoogle Scholar
  8. 8.
    Pfister, O., Mouquet, F., Jain, M., Summer, R., Helmes, M., Fine, A., Colucci, W. S., & Liao, R. (2005). CD31-but Not CD31+ cardiac side population cells exhibit functional cardiomyogenic differentiation. Circulation Research, 97, 52–61.PubMedGoogle Scholar
  9. 9.
    Oh, H., Bradfute, S. B., Gallardo, T. D., Nakamura, T., Gaussin, V., Mishina, Y., Pocius, J., Michael, L. H., Behringer, R. R., Garry, D. J., Entman, M. L., & Schneider, M. D. (2003). Cardiac progenitor cells from adult myocardium: Homing, differentiation, and fusion after infarction. Proceedings of the National Academy of Sciences of the United States of America, 100, 12313–12318.PubMedGoogle Scholar
  10. 10.
    Rubart, M., & Field, L. J. (2006). Cardiac regeneration: Repopulating the heart. Annual Review of Physiology, 68, 29–49.PubMedGoogle Scholar
  11. 11.
    Murry, C. E., Field, L. J., & Menasche, P. (2005). Cell-based cardiac repair: Reflections at the 10-year point. Circulation, 112, 3174–3183.PubMedGoogle Scholar
  12. 12.
    Chen, X., Wilson, R. M., Kubo, H., Berretta, R. M., Harris, D. M., Zhang, X., Jaleel, N., MacDonnell, S. M., Bearzi, C., Tillmanns, J., Trofimova, I., Hosoda, T., Mosna, F., Cribbs, L., Leri, A., Kajstura, J., Anversa, P., & Houser, S. R. (2007). Adolescent feline heart contains a population of small, proliferative ventricular myocytes with immature physiological properties. Circulation Research, 100, 536–544.PubMedGoogle Scholar
  13. 13.
    Bearzi, C., Rota, M., Hosoda, T., Tillmanns, J., Nascimbene, A., De Angelis, A., Yasuzawa-Amano, S., Trofimova, I., Siggins, R. W., Lecapitaine, N., Cascapera, S., Beltrami, A. P., D’Alessandro, D. A., Zias, E., Quaini, F., Urbanek, K., Michler, R. E., Bolli, R., Kajstura, J., Leri, A., & Anversa, P. (2007). Human cardiac stem cells. Proceedings of the National Academy of Sciences of the United States of America, 104, 14068–14073.PubMedGoogle Scholar
  14. 14.
    Beltrami, A. P., Barlucchi, L., Torella, D., Baker, M., Limana, F., Chimenti, S., Kasahara, H., Rota, M., Musso, E., Urbanek, K., Leri, A., Kajstura, J., Nadal-Ginard, B., & Anversa, P. (2003). Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell, 114, 763–776.PubMedGoogle Scholar
  15. 15.
    Soonpaa, M. H., & Field, L. J. (1997). Assessment of cardiomyocyte DNA synthesis in normal and injured adult mouse hearts. American Journal of Physiology, 272, H220–226.PubMedGoogle Scholar
  16. 16.
    Smith, R. R., Barile, L., Cho, H. C., Leppo, M. K., Hare, J. M., Messina, E., Giacomello, A., Abraham, M. R., & Marban, E. (2007). Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation, 115, 896–908.PubMedGoogle Scholar
  17. 17.
    Messina, E., De Angelis, L., Frati, G., Morrone, S., Chimenti, S., Fiordaliso, F., Salio, M., Battaglia, M., Latronico, M. V., Coletta, M., Vivarelli, E., Frati, L., Cossu, G., & Giacomello, A. (2004). Isolation and expansion of adult cardiac stem cells from human and murine heart. Circulation Research, 95, 911–921.PubMedGoogle Scholar
  18. 18.
    Barile, L., Messina, E., Giacomello, A., & Marban, E. (2007). Endogenous cardiac stem cells. Progress in Cardiovascular Diseases, 50, 31–48.PubMedGoogle Scholar
  19. 19.
    Yau, T. M., Kim, C., Ng, D., Li, G., Zhang, Y., Weisel, R. D., & Li, R. K. (2005). Increasing transplanted cell survival with cell-based angiogenic gene therapy. Annals of Thoracic Surgery, 80, 1779–1786.PubMedGoogle Scholar
  20. 20.
    Caspi, O., Lesman, A., Basevitch, Y., Gepstein, A., Arbel, G., Habib, I. H., Gepstein, L., & Levenberg, S. (2007). Tissue engineering of vascularized cardiac muscle from human embryonic stem cells. Circulation Research, 100, 263–272.PubMedGoogle Scholar
  21. 21.
    Menasche, P. (2003). Skeletal muscle satellite cell transplantation. Cardiovascular Research, 58, 351–357.PubMedGoogle Scholar
  22. 22.
    Taylor, D. A., Atkins, B. Z., Hungspreugs, P., Jones, T. R., Reedy, M. C., Hutcheson, K. A., Glower, D. D., & Kraus, W. E. (1998). Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nature Medicine, 4, 929–933.PubMedGoogle Scholar
  23. 23.
    Murry, C. E., Wiseman, R. W., Schwartz, S. M., & Hauschka, S. D. (1996). Skeletal myoblast transplantation for repair of myocardial necrosis. Journal of Clinical Investigation, 98, 2512–2523.PubMedGoogle Scholar
  24. 24.
    Menasche, P., Hagege, A. A., Vilquin, J. T., Desnos, M., Abergel, E., Pouzet, B., Bel, A., Sarateanu, S., Scorsin, M., Schwartz, K., Bruneval, P., Benbunan, M., Marolleau, J. P., & Duboc, D. (2003). Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. Journal of the American College of Cardiology, 41, 1078–1083.PubMedGoogle Scholar
  25. 25.
    Leobon, B., Garcin, I., Menasche, P., Vilquin, J. T., Audinat, E., & Charpak, S. (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, 7808–7811.PubMedGoogle Scholar
  26. 26.
    Abraham, M. R., Henrikson, C. A., Tung, L., Chang, M. G., Aon, M., Xue, T., Li, R. A., O’Rourke, B., & Marban, E. (2005). Antiarrhythmic engineering of skeletal myoblasts for cardiac transplantation. Circulation Research, 97, 159–167.PubMedGoogle Scholar
  27. 27.
    Orlic, D., Kajstura, J., Chimenti, S., Jakoniuk, I., Anderson, S. M., Li, B., Pickel, J., McKay, R., Nadal-Ginard, B., Bodine, D. M., Leri, A., & Anversa, P. (2001). Bone marrow cells regenerate infarcted myocardium. Nature, 410, 701–705.PubMedGoogle Scholar
  28. 28.
    Alvarez-Dolado, M., Pardal, R., Garcia-Verdugo, J. M., Fike, J. R., Lee, H. O., Pfeffer, K., Lois, C., Morrison, S. J., & Alvarez-Buylla, A. (2003). Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature, 425, 968–973.PubMedGoogle Scholar
  29. 29.
    Balsam, L. B., Wagers, A. J., Christensen, J. L., Kofidis, T., Weissman, I. L., & Robbins, R. C. (2004). Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature, 428, 668–673.PubMedGoogle Scholar
  30. 30.
    Nygren, J. M., Jovinge, S., Breitbach, M., Sawen, P., Roll, W., Hescheler, J., Taneera, J., Fleischmann, B. K., & Jacobsen, S. E. (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
  31. 31.
    Kajstura, J., Rota, M., Whang, B., Cascapera, S., Hosoda, T., Bearzi, C., Nurzynska, D., Kasahara, H., Zias, E., Bonafe, M., Nadal-Ginard, B., Torella, D., Nascimbene, A., Quaini, F., Urbanek, K., Leri, A., & Anversa, P. (2005). Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion. Circulation Research, 96, 127–137.PubMedGoogle Scholar
  32. 32.
    Chen, S. L., Fang, W. W., Ye, F., Liu, Y. H., Qian, J., Shan, S. J., Zhang, J. J., Chunhua, R. Z., Liao, L. M., Lin, S., & Sun, J. P. (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, 92–95.PubMedGoogle Scholar
  33. 33.
    Wollert, K. C., Meyer, G. P., Lotz, J., Ringes-Lichtenberg, S., Lippolt, P., Breidenbach, C., Fichtner, S., Korte, T., Hornig, B., Messinger, D., Arseniev, L., Hertenstein, B., Ganser, A., & Drexler, H. (2004). Intracoronary autologous bone-marrow cell transfer after myocardial infarction: The BOOST randomised controlled clinical trial. Lancet, 364, 141–148.PubMedGoogle Scholar
  34. 34.
    Shake, J. G., Gruber, P. J., Baumgartner, W. A., Senechal, G., Meyers, J., Redmond, J. M., Pittenger, M. F., & Martin, B. J. (2002). Mesenchymal stem cell implantation in a swine myocardial infarct model: Engraftment and functional effects. Annals of Thoracic Surgery, 73, 1919–1925, discussion 1926.PubMedGoogle Scholar
  35. 35.
    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
  36. 36.
    Grauss, R. W., Winter, E. M., van Tuyn, J., Pijnappels, D. A., Vicente Steijn, R., Hogers, B., van der Geest, R., de Vries, A. A., Steendijk, P., van der Laarse, A., Gittenberger-de Groot, A. C., Schalij, M. J., & Atsma, D. E. (2007). Mesenchymal stem cells from ischemic heart disease patients improve left ventricular function after acute myocardial infarction. American Journal of Physiology. Heart and Circulatory Physiology, 293, H2438–H2447.PubMedGoogle Scholar
  37. 37.
    Zeng, L., Hu, Q., Wang, X., Mansoor, A., Lee, J., Feygin, J., Zhang, G., Suntharalingam, P., Boozer, S., Mhashilkar, A., Panetta, C. J., Swingen, C., Deans, R., From, A. H., Bache, R. J., Verfaillie, C. M., & Zhang, J. (2007). Bioenergetic and functional consequences of bone marrow-derived multipotent progenitor cell transplantation in hearts with postinfarction left ventricular remodeling. Circulation, 115, 1866–1875.PubMedGoogle Scholar
  38. 38.
    Kinnaird, T., Stabile, E., Burnett, M. S., Shou, M., Lee, C. W., Barr, S., Fuchs, S., & Epstein, S. E. (2004). Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation, 109, 1543–1549.PubMedGoogle Scholar
  39. 39.
    Tang, J., Xie, Q., Pan, G., Wang, J., & Wang, M. (2006). Mesenchymal stem cells participate in angiogenesis and improve heart function in rat model of myocardial ischemia with reperfusion. European Journal of Cardiothoracic Surgery, 30, 353–361.PubMedGoogle Scholar
  40. 40.
    Tang, Y. L., Zhao, Q., Qin, X., Shen, L., Cheng, L., Ge, J., & Phillips, M. I. (2005). Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction. Annals of Thoracic Surgery, 80, 229–236, discussion 236–227.PubMedGoogle Scholar
  41. 41.
    Yoon, Y. S., Wecker, A., Heyd, L., Park, J. S., Tkebuchava, T., Kusano, K., Hanley, A., Scadova, H., Qin, G., Cha, D. H., Johnson, K. L., Aikawa, R., Asahara, T., & Losordo, D. W. (2005). Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. Journal of Clinical Investigation, 115, 326–338.PubMedGoogle Scholar
  42. 42.
    Piao, H., Youn, T. J., Kwon, J. S., Kim, Y. H., Bae, J. W., Bora, S., Kim, D. W., Cho, M. C., Lee, M. M., & Park, Y. B. (2005). Effects of bone marrow derived mesenchymal stem cells transplantation in acutely infarcting myocardium. European Journal of Heart Failure, 7, 730–738.PubMedGoogle Scholar
  43. 43.
    Ohnishi, S., Sumiyoshi, H., Kitamura, S., & Nagaya, N. (2007). Mesenchymal stem cells attenuate cardiac fibroblast proliferation and collagen synthesis through paracrine actions. FEBS Letters, 581, 3961–3966.PubMedGoogle Scholar
  44. 44.
    Mangi, A. A., Noiseux, N., Kong, D., He, H., Rezvani, M., Ingwall, J. S., & Dzau, V. J. (2003). Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nature Medicine, 9, 1195–1201.PubMedGoogle Scholar
  45. 45.
    Gnecchi, M., He, H., Liang, O. D., Melo, L. G., Morello, F., Mu, H., Noiseux, N., Zhang, L., Pratt, R. E., Ingwall, J. S., & Dzau, V. J. (2005). Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nature Medicine, 11, 367–368.PubMedGoogle Scholar
  46. 46.
    Kawai, T., Takahashi, T., Esaki, M., Ushikoshi, H., Nagano, S., Fujiwara, H., & Kosai, K. (2004). Efficient cardiomyogenic differentiation of embryonic stem cell by fibroblast growth factor 2 and bone morphogenetic protein 2. Circulation Journal, 68, 691–702.PubMedGoogle Scholar
  47. 47.
    Yuasa, S., Itabashi, Y., Koshimizu, U., Tanaka, T., Sugimura, K., Kinoshita, M., Hattori, F., Fukami, S., Shimazaki, T., Ogawa, S., Okano, H., & Fukuda, K. (2005). Transient inhibition of BMP signaling by Noggin induces cardiomyocyte differentiation of mouse embryonic stem cells. Nature Biotechnology, 23, 607–611.PubMedGoogle Scholar
  48. 48.
    Bakunts, K., Gillum, N., Karabekian, Z., Sarvazyan, N. (2007). Formation of cardiac fibers in matrigel matrix. Biotechniques, In press.Google Scholar
  49. 49.
    Laflamme, M. A., Chen, K. Y., Naumova, A. V., Muskheli, V., Fugate, J. A., Dupras, S. K., Reinecke, H., Xu, C., Hassanipour, M., Police, S., O’Sullivan, C., Collins, L., Chen, Y., Minami, E., Gill, E. A., Ueno, S., Yuan, C., Gold, J., & Murry, C. E. (2007). Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nature Biotechnology, 25, 1015–1024.PubMedGoogle Scholar
  50. 50.
    Wobus, A. M., Wallukat, G., & Hescheler, J. (1991). Pluripotent mouse embryonic stem cells are able to differentiate into cardiomyocytes expressing chronotropic responses to adrenergic and cholinergic agents and Ca2+ channel blockers. Differentiation, 48, 173–182.PubMedGoogle Scholar
  51. 51.
    Kehat, I., Kenyagin-Karsenti, D., Snir, M., Segev, H., Amit, M., Gepstein, A., Livne, E., Binah, O., Itskovitz-Eldor, J., & Gepstein, L. (2001). Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. Journal of Clinical Investigation, 108, 407–414.PubMedGoogle Scholar
  52. 52.
    Boheler, K. R., Czyz, J., Tweedie, D., Yang, H. T., Anisimov, S. V., & Wobus, A. M. (2002). Differentiation of pluripotent embryonic stem cells into cardiomyocytes. Circulation Research, 91, 189–201.PubMedGoogle Scholar
  53. 53.
    Nussbaum, J., Minami, E., Laflamme, M. A., Virag, J. A., Ware, C. B., Masino, A., Muskheli, V., Pabon, L., Reinecke, H., & Murry, C. E. (2007). Transplantation of undifferentiated murine embryonic stem cells in the heart: Teratoma formation and immune response. FASEB Journal, 21, 1345–1357.PubMedGoogle Scholar
  54. 54.
    Leor, J., Gerecht-Nir, S., Cohen, S., Miller, L., Holbova, R., Ziskind, A., Shachar, M., Feinberg, M. S., Guetta, E., & Itskovitz-Eldor, J. (2007). Human embryonic stem cell transplantation to repair the infarcted myocardium. Heart, 93, 1278–1284.PubMedGoogle Scholar
  55. 55.
    Kolossov, E., Bostani, T., Roell, W., Breitbach, M., Pillekamp, F., Nygren, J. M., Sasse, P., Rubenchik, O., Fries, J. W., Wenzel, D., Geisen, C., Xia, Y., Lu, Z., Duan, Y., Kettenhofen, R., Jovinge, S., Bloch, W., Bohlen, H., Welz, A., Hescheler, J., Jacobsen, S. E., & Fleischmann, B. K. (2006). Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium. Journal of Experimental Medicine, 203, 2315–2327.PubMedGoogle Scholar
  56. 56.
    Zandstra, P. W., Bauwens, C., Yin, T., Liu, Q., Schiller, H., Zweigerdt, R., Pasumarthi, K. B., & Field, L. J. (2003). Scalable production of embryonic stem cell-derived cardiomyocytes. Tissue Engineering, 9, 767–778.PubMedGoogle Scholar
  57. 57.
    Huber, I., Itzhaki, I., Caspi, O., Arbel, G., Tzukerman, M., Gepstein, A., Habib, M., Yankelson, L., Kehat, I., & Gepstein, L. (2007). Identification and selection of cardiomyocytes during human embryonic stem cell differentiation. FASEB Journal, 21, 2551–2563.PubMedGoogle Scholar
  58. 58.
    E, L. L., Zhao, Y. S., Guo, X. M., Wang, C. Y., Jiang, H., Li, J., Duan, C. M., & Song, Y. (2006). Enrichment of cardiomyocytes derived from mouse embryonic stem cells. Journal of Heart and Lung Transplantation, 25, 664–674.PubMedGoogle Scholar
  59. 59.
    Xu, C., Police, S., Hassanipour, M., & Gold, J. D. (2006). Cardiac bodies: A novel culture method for enrichment of cardiomyocytes derived from human embryonic stem cells. Stem Cells and Development, 15, 631–639.PubMedGoogle Scholar
  60. 60.
    Wobus, A. M., Kaomei, G., Shan, J., Wellner, M. C., Rohwedel, J., Ji, G., Fleischmann, B., Katus, H. A., Hescheler, J., & Franz, W. M. (1997). Retinoic acid accelerates embryonic stem cell-derived cardiac differentiation and enhances development of ventricular cardiomyocytes. Journal of Molecular and Cellular Cardiology, 29, 1525–1539.PubMedGoogle Scholar
  61. 61.
    Takahashi, T., Lord, B., Schulze, P. C., Fryer, R. M., Sarang, S. S., Gullans, S. R., & Lee, R. T. (2003). Ascorbic acid enhances differentiation of embryonic stem cells into cardiac myocytes. Circulation, 107, 1912–1916.PubMedGoogle Scholar
  62. 62.
    Behfar, A., Zingman, L. V., Hodgson, D. M., Rauzier, J. M., Kane, G. C., Terzic, A., & Puceat, M. (2002). Stem cell differentiation requires a paracrine pathway in the heart. FASEB Journal, 16, 1558–1566.PubMedGoogle Scholar
  63. 63.
    Loebel, D. A., Watson, C. M., De Young, R. A., & Tam, P. P. (2003). Lineage choice and differentiation in mouse embryos and embryonic stem cells. Developmental Biology, 264, 1–14.PubMedGoogle Scholar
  64. 64.
    Menard, C., Hagege, A. A., Agbulut, O., Barro, M., Morichetti, M. C., Brasselet, C., Bel, A., Messas, E., Bissery, A., Bruneval, P., Desnos, M., Puceat, M., & Menasche, P. (2005). Transplantation of cardiac-committed mouse embryonic stem cells to infarcted sheep myocardium: A preclinical study. Lancet, 366, 1005–1012.PubMedGoogle Scholar
  65. 65.
    Laflamme, M. A., Gold, J., Xu, C., Hassanipour, M., Rosler, E., Police, S., Muskheli, V., & Murry, C. E. (2005). Formation of human myocardium in the rat heart from human embryonic stem cells. American Journal of Pathology, 167, 663–671.PubMedGoogle Scholar
  66. 66.
    Naito, H., Melnychenko, I., Didie, M., Schneiderbanger, K., Schubert, P., Rosenkranz, S., Eschenhagen, T., & Zimmermann, W. H. (2006). Optimizing engineered heart tissue for therapeutic applications as surrogate heart muscle. Circulation, 114, I72–78.PubMedGoogle Scholar
  67. 67.
    Singla, D. K., Lyons, G. E., & Kamp, T. J. (2007). Transplanted embryonic stem cells following mouse myocardial infarction inhibit apoptosis and cardiac remodeling. American Journal of Physiology. Heart and Circulatory Physiology, 293, H1308–1314.PubMedGoogle Scholar
  68. 68.
    Hao, J., Ju, H., Zhao, S., Junaid, A., Scammell-La Fleur, T., & Dixon, I. M. (1999). Elevation of expression of Smads 2, 3, and 4, decorin and TGF-beta in the chronic phase of myocardial infarct scar healing. Journal of Molecular and Cellular Cardiology, 31, 667–678.PubMedGoogle Scholar
  69. 69.
    Singla, D. K., & McDonald, D. E. (2007). Factors released from embryonic stem cells inhibit apoptosis of H9c2 cells. American Journal of Physiology. Heart and Circulatory Physiology, 293, H1590–1595.PubMedGoogle Scholar
  70. 70.
    Min, J. Y., Huang, X., Xiang, M., Meissner, A., Chen, Y., Ke, Q., Kaplan, E., Rana, J. S., Oettgen, P., & Morgan, J. P. (2006). Homing of intravenously infused embryonic stem cell-derived cells to injured hearts after myocardial infarction. Journal of Thoracic and Cardiovascular Surgery, 131, 889–897.PubMedGoogle Scholar
  71. 71.
    Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131, 861–872.PubMedGoogle Scholar
  72. 72.
    Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., Nie, J., Jonsdottir, G. A., Ruotti, V., Stewart, R., Slukvin, II, & Thomson, J. A. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science.Google Scholar
  73. 73.
    Zimmermann, W. H., Fink, C., Kralisch, D., Remmers, U., Weil, J., & Eschenhagen, T. (2000). Three-dimensional engineered heart tissue from neonatal rat cardiac myocytes. Biotechnology and Bioengineering, 68, 106–114.PubMedGoogle Scholar
  74. 74.
    Zimmermann, W. H., Melnychenko, I., Wasmeier, G., Didie, M., Naito, H., Nixdorff, U., Hess, A., Budinsky, L., Brune, K., Michaelis, B., Dhein, S., Schwoerer, A., Ehmke, H., & Eschenhagen, T. (2006). Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts. Nature Medicine, 12, 452–458.PubMedGoogle Scholar
  75. 75.
    Shimizu, T., Yamato, M., Isoi, Y., Akutsu, T., Setomaru, T., Abe, K., Kikuchi, A., Umezu, M., & Okano, T. (2002). Fabrication of pulsatile cardiac tissue grafts using a novel 3-dimensional cell sheet manipulation technique and temperature-responsive cell culture surfaces. Circulation Research, 90, e40.PubMedGoogle Scholar
  76. 76.
    Furuta, A., Miyoshi, S., Itabashi, Y., Shimizu, T., Kira, S., Hayakawa, K., Nishiyama, N., Tanimoto, K., Hagiwara, Y., Satoh, T., Fukuda, K., Okano, T., & Ogawa, S. (2006). Pulsatile cardiac tissue grafts using a novel three-dimensional cell sheet manipulation technique functionally integrates with the host heart, in vivo. Circulation Research, 98, 705–712.PubMedGoogle Scholar
  77. 77.
    Gerecht-Nir, S., Radisic, M., Park, H., Cannizzaro, C., Boublik, J., Langer, R., & Vunjak-Novakovic, G. (2006). Biophysical regulation during cardiac development and application to tissue engineering. International Journal of Developmental Biology, 50, 233–243.PubMedGoogle Scholar
  78. 78.
    Liu, Y. P., Dovzhenko, O. V., Garthwaite, M. A., Dambaeva, S. V., Durning, M., Pollastrini, L. M., & Golos, T. G. (2004). Maintenance of pluripotency in human embryonic stem cells stably over-expressing enhanced green fluorescent protein. Stem Cells and Development, 13, 636–645.PubMedGoogle Scholar
  79. 79.
    Hodgson, D. M., Behfar, A., Zingman, L. V., Kane, G. C., Perez-Terzic, C., Alekseev, A. E., Puceat, M., & Terzic, A. (2004). Stable benefit of embryonic stem cell therapy in myocardial infarction. American Journal of Physiology. Heart and Circulatory Physiology, 287, H471–479.PubMedGoogle Scholar
  80. 80.
    Kofidis, T., de Bruin, J. L., Yamane, T., Tanaka, M., Lebl, D. R., Swijnenburg, R. J., Weissman, I. L., & Robbins, R. C. (2005). Stimulation of paracrine pathways with growth factors enhances embryonic stem cell engraftment and host-specific differentiation in the heart after ischemic myocardial injury. Circulation, 111, 2486–2493.PubMedGoogle Scholar
  81. 81.
    Xue, T., Cho, H. C., Akar, F. G., Tsang, S. Y., Jones, S. P., Marban, E., Tomaselli, G. F., & Li, R. A. (2005). Functional integration of electrically active cardiac derivatives from genetically engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes: Insights into the development of cell-based pacemakers. Circulation, 111, 11–20.PubMedGoogle Scholar
  82. 82.
    Behfar, A., Perez-Terzic, C., Faustino, R. S., Arrell, D. K., Hodgson, D. M., Yamada, S., Puceat, M., Niederlander, N., Alekseev, A. E., Zingman, L. V., & Terzic, A. (2007). Cardiopoietic programming of embryonic stem cells for tumor-free heart repair. Journal of Experimental Medicine, 204, 405–420.PubMedGoogle Scholar
  83. 83.
    Kehat, I., Khimovich, L., Caspi, O., Gepstein, A., Shofti, R., Arbel, G., Huber, I., Satin, J., Itskovitz-Eldor, J., & Gepstein, L. (2004). Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nature Biotechnology, 22, 1282–1289.PubMedGoogle Scholar
  84. 84.
    van Laake, L. W., Hassink, R., Doevendans, P. A., & Mummery, C. (2006). Heart repair and stem cells. Journal of Physiology, 577, 467–478.PubMedGoogle Scholar
  85. 85.
    Mummery, C., Ward-van Oostwaard, D., Doevendans, P., Spijker, R., van den Brink, S., Hassink, R., van der Heyden, M., Opthof, T., Pera, M., de la Riviere, A. B., Passier, R., & Tertoolen, L. (2003). Differentiation of human embryonic stem cells to cardiomyocytes: role of coculture with visceral endoderm-like cells. Circulation, 107, 2733–2740.PubMedGoogle Scholar
  86. 86.
    Halbach, M., Pfannkuche, K., Pillekamp, F., Ziomka, A., Hannes, T., Reppel, M., Hescheler, J., & Muller-Ehmsen, J. (2007). Electrophysiological maturation and integration of murine fetal cardiomyocytes after transplantation. Circulation Research, 101, 484–492.PubMedGoogle Scholar
  87. 87.
    Chang, M. G., Tung, L., Sekar, R. B., Chang, C. Y., Cysyk, J., Dong, P., Marban, E., & Abraham, M. R. (2006). Proarrhythmic potential of mesenchymal stem cell transplantation revealed in an in vitro coculture model. Circulation, 113, 1832–1841.PubMedGoogle Scholar
  88. 88.
    Zhang, Y. M., Hartzell, C., Narlow, M., & Dudley, S. C. Jr (2002). Stem cell-derived cardiomyocytes demonstrate arrhythmic potential. Circulation, 106, 1294–1299.PubMedGoogle Scholar
  89. 89.
    Dolnikov, K., Shilkrut, M., Zeevi-Levin, N., Danon, A., Gerecht-Nir, S., Itskovitz-Eldor, J., & Binah, O. (2005). Functional properties of human embryonic stem cell-derived cardiomyocytes. Annals of the New York Academy of Sciences, 1047, 66–75.PubMedGoogle Scholar
  90. 90.
    Dolnikov, K., Shilkrut, M., Zeevi-Levin, N., Gerecht-Nir, S., Amit, M., Danon, A., Itskovitz-Eldor, J., & Binah, O. (2006). Functional properties of human embryonic stem cell-derived cardiomyocytes: Intracellular Ca2+ handling and the role of sarcoplasmic reticulum in the contraction. Stem Cells, 24, 236–245.PubMedGoogle Scholar
  91. 91.
    Viatchenko-Karpinski, S., Fleischmann, B. K., Liu, Q., Sauer, H., Gryshchenko, O., Ji, G. J., & Hescheler, J. (1999). Intracellular Ca2+ oscillations drive spontaneous contractions in cardiomyocytes during early development. Proceedings of the National Academy of Sciences of the United States of America, 96, 8259–8264.PubMedGoogle Scholar
  92. 92.
    Satin, J., Kehat, I., Caspi, O., Huber, I., Arbel, G., Itzhaki, I., Magyar, J., Schroder, E. A., Perlman, I., & Gepstein, L. (2004). Mechanism of spontaneous excitability in human embryonic stem cell derived cardiomyocytes. Journal of Physiology, 559, 479–496.PubMedGoogle Scholar
  93. 93.
    Snir, M., Kehat, I., Gepstein, A., Coleman, R., Itskovitz-Eldor, J., Livne, E., & Gepstein, L. (2003). Assessment of the ultrastructural and proliferative properties of human embryonic stem cell-derived cardiomyocytes. American Journal of Physiology. Heart and Circulatory Physiology, 285, H2355–2363.PubMedGoogle Scholar
  94. 94.
    Yang, H. T., Tweedie, D., Wang, S., Guia, A., Vinogradova, T., Bogdanov, K., Allen, P. D., Stern, M. D., Lakatta, E. G., & Boheler, K. R. (2002). The ryanodine receptor modulates the spontaneous beating rate of cardiomyocytes during development. Proceedings of the National Academy of Sciences of the United States of America, 99, 9225–9230.PubMedGoogle Scholar
  95. 95.
    Sauer, H., Theben, T., Hescheler, J., Lindner, M., Brandt, M. C., & Wartenberg, M. (2001). Characteristics of calcium sparks in cardiomyocytes derived from embryonic stem cells. American Journal of Physiology. Heart and Circulatory Physiology, 281, H411–421.PubMedGoogle Scholar
  96. 96.
    Makowski, L., Caspar, D. L., Phillips, W. C., & Goodenough, D. A. (1977). Gap junction structures II. Analysis of the X-ray diffraction data. Journal of Cell Biology, 74, 629–645.PubMedGoogle Scholar
  97. 97.
    Guerrero, P. A., Schuessler, R. B., Davis, L. M., Beyer, E. C., Johnson, C. M., Yamada, K. A., & Saffitz, J. E. (1997). Slow ventricular conduction in mice heterozygous for a connexin43 null mutation. Journal of Clinical Investigation, 99, 1991–1998.PubMedGoogle Scholar
  98. 98.
    Saez, J. C., Berthoud, V. M., Branes, M. C., Martinez, A. D., & Beyer, E. C. (2003). Plasma membrane channels formed by connexins: Their regulation and functions. Physiological Review, 83, 1359–1400.Google Scholar
  99. 99.
    Gallicano, G. I., Kouklis, P., Bauer, C., Yin, M., Vasioukhin, V., Degenstein, L., & Fuchs, E. (1998). Desmoplakin is required early in development for assembly of desmosomes and cytoskeletal linkage. Journal Cell Biology, 143, 2009–2022.Google Scholar
  100. 100.
    Linask, K. K., Knudsen, K. A., & Gui, Y. H. (1997). N-cadherin–catenin interaction: necessary component of cardiac cell compartmentalization during early vertebrate heart development. Developmental Biology, 185, 148–164.PubMedGoogle Scholar
  101. 101.
    Ozawa, M., Ringwald, M., & Kemler, R. (1990). Uvomorulin-catenin complex formation is regulated by a specific domain in the cytoplasmic region of the cell adhesion molecule. Proceedings of the National Academy of Sciences of the United States of America, 87, 4246–4250.PubMedGoogle Scholar
  102. 102.
    Staehelin, L. A. (1974). Structure and function of intercellular junctions. International Review of Cytology, 39, 191–283.PubMedCrossRefGoogle Scholar
  103. 103.
    Rimm, D. L., Koslov, E. R., Kebriaei, P., Cianci, C. D., & Morrow, J. S. (1995). Alpha 1(E)-catenin is an actin-binding and -bundling protein mediating the attachment of F-actin to the membrane adhesion complex. Proceedings of the National Academy of Sciences of the United States of America, 92, 8813–8817.PubMedGoogle Scholar
  104. 104.
    Hertig, C. M., Butz, S., Koch, S., Eppenberger-Eberhardt, M., Kemler, R., & Eppenberger, H. M. (1996). N-cadherin in adult rat cardiomyocytes in culture II. Spatio-temporal appearance of proteins involved in cell-cell contact and communication. Formation of two distinct N-cadherin/catenin complexes. Journal of Cell Science, 109(Pt 1), 11–20.PubMedGoogle Scholar
  105. 105.
    Gutstein, D. E., Liu, F. Y., Meyers, M. B., Choo, A., & Fishman, G. I. (2003). The organization of adherens junctions and desmosomes at the cardiac intercalated disc is independent of gap junctions. Journal of Cell Science, 116, 875–885.PubMedGoogle Scholar
  106. 106.
    Kostin, S., Hein, S., Bauer, E. P., & Schaper, J. (1999). Spatiotemporal development and distribution of intercellular junctions in adult rat cardiomyocytes in culture. Circulation Research, 85, 154–167.PubMedGoogle Scholar
  107. 107.
    Zuppinger, C., Schaub, M. C., & Eppenberger, H. M. (2000). Dynamics of early contact formation in cultured adult rat cardiomyocytes studied by N-cadherin fused to green fluorescent protein. Journal of Molecular and Cell Cardiology, 32, 539–555.Google Scholar
  108. 108.
    Radice, G. L., Rayburn, H., Matsunami, H., Knudsen, K. A., Takeichi, M., & Hynes, R. O. (1997). Developmental defects in mouse embryos lacking N-cadherin. Developmental Biology, 181, 64–78.PubMedGoogle Scholar
  109. 109.
    Kostetskii, I., Li, J., Xiong, Y., Zhou, R., Ferrari, V. A., Patel, V. V., Molkentin, J. D., & Radice, G. L. (2005). Induced deletion of the N-cadherin gene in the heart leads to dissolution of the intercalated disc structure. Circulation Research, 96, 346–354.PubMedGoogle Scholar
  110. 110.
    Li, J., Patel, V. V., Kostetskii, I., Xiong, Y., Chu, A. F., Jacobson, J. T., Yu, C., Morley, G. E., Molkentin, J. D., & Radice, G. L. (2005). Cardiac-specific loss of N-cadherin leads to alteration in connexins with conduction slowing and arrhythmogenesis. Circulation Research, 97, 474–481.PubMedGoogle Scholar
  111. 111.
    Reaume, A. G., de Sousa, P. A., Kulkarni, S., Langille, B. L., Zhu, D., Davies, T. C., Juneja, S. C., Kidder, G. M., & Rossant, J. (1995). Cardiac malformation in neonatal mice lacking connexin43. Science, 267, 1831–1834.PubMedGoogle Scholar
  112. 112.
    Gutstein, D. E., Morley, G. E., Tamaddon, H., Vaidya, D., Schneider, M. D., Chen, J., Chien, K. R., Stuhlmann, H., & Fishman, G. I. (2001). Conduction slowing and sudden arrhythmic death in mice with cardiac-restricted inactivation of connexin43. Circulation Research, 88, 333–339.PubMedGoogle Scholar
  113. 113.
    van Rijen, H. V., Eckardt, D., Degen, J., Theis, M., Ott, T., Willecke, K., Jongsma, H. J., Opthof, T., & de Bakker, J. M. (2004). Slow conduction and enhanced anisotropy increase the propensity for ventricular tachyarrhythmias in adult mice with induced deletion of connexin43. Circulation, 109, 1048–1055.PubMedGoogle Scholar
  114. 114.
    Lerner, D. L., Yamada, K. A., Schuessler, R. B., & Saffitz, J. E. (2000). Accelerated onset and increased incidence of ventricular arrhythmias induced by ischemia in Cx43-deficient mice. Circulation, 101, 547–552.PubMedGoogle Scholar
  115. 115.
    Eckardt, D., Theis, M., Degen, J., Ott, T., van Rijen, H. V., Kirchhoff, S., Kim, J. S., de Bakker, J. M., & Willecke, K. (2004). Functional role of connexin43 gap junction channels in adult mouse heart assessed by inducible gene deletion. Journal of Molecular and Cell Cardiology, 36, 101–110.Google Scholar
  116. 116.
    Wahl, J. K. 3rd, Kim, Y. J., Cullen, J. M., Johnson, K. R., & Wheelock, M. J. (2003). N-cadherin–catenin complexes form prior to cleavage of the proregion and transport to the plasma membrane. Journal of Biological Chemistry, 278, 17269–17276.PubMedGoogle Scholar
  117. 117.
    Thoreson, M. A., Anastasiadis, P. Z., Daniel, J. M., Ireton, R. C., Wheelock, M. J., Johnson, K. R., Hummingbird, D. K., & Reynolds, A. B. (2000). Selective uncoupling of p120(ctn) from E-cadherin disrupts strong adhesion. Journal of Cell Biology, 148, 189–202.PubMedGoogle Scholar
  118. 118.
    Davis, M. A., Ireton, R. C., & Reynolds, A. B. (2003). A core function for p120-catenin in cadherin turnover. Journal of Cell Biology, 163, 525–534.PubMedGoogle Scholar
  119. 119.
    Ferreira-Cornwell, M. C., Luo, Y., Narula, N., Lenox, J. M., Lieberman, M., & Radice, G. L. (2002). Remodeling the intercalated disc leads to cardiomyopathy in mice misexpressing cadherins in the heart. Journal of Cell Science, 115, 1623–1634.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  1. 1.Pharmacology and Physiology DepartmentThe George Washington UniversityWashingtonUSA

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