Human embryonic stem cell-derived cardiomyocytes: Therapeutic potentials and limitations

Journal of Stem Cells

Volumn 1, Issue 2, 2006, Pages 109-124

  Li, Ronald A ^a   Moore, Jennifer C ^a   Tarasova, Yelena S ^b   Boheler, Kenneth R ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b NATIONAL INSTITUTE ON AGING   (United States)

Author keywords

Cardiomyocytes; Differentiation; Embryonic stem cells; Human; Pacemaker

Indexed keywords

4 (N ETHYL N PHENYLAMINO) 1,2 DIMETHYL 6 (METHYLAMINO)PYRIMIDINIUM CHLORIDE; BONE MORPHOGENETIC PROTEIN 2; GENE PRODUCT; LIDOCAINE; PROTEIN HCN; TRANSCRIPTION FACTOR NKX2.5; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; WNT PROTEIN;

BLASTOCYST; CELL DIFFERENTIATION; CELL LINE; CELL LINEAGE; CELL REGENERATION; CELL RENEWAL; CELL THERAPY; CELL TRANSPLANTATION; CELL VIABILITY; DEVELOPMENTAL BIOLOGY; EMBRYO DEVELOPMENT; EMBRYONIC STEM CELL; GENE TRANSFER; GERM LAYER; HEART DEVELOPMENT; HEART DISEASE; HEART INFARCTION; HEART MUSCLE CELL; HEART TRANSPLANTATION; HUMAN; INNER CELL MASS; MOLECULAR BIOLOGY; MULTIPOTENT STEM CELL; NONHUMAN; PACEMAKER; PLURIPOTENT STEM CELL; REVIEW; SPECIES DIFFERENCE;

EID: 34247098043     PISSN: 15568539     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (97)

1. Evans, M. J. and Kaufman, M. H. Establishment in Culture of Pluripotential Cells from Mouse Embryos. Nature, 1981, 292, 154-156.
2. Martin, G. R. Isolation of a Pluripotent Cell Line from Early Mouse Embryos Cultured in Medium Conditioned by Teratocarcinoma Stem Cells. Proc.Natl.Acad.Sci.U.S.A., 1981, 78, 7634-7638.
3. Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S. and Jones, J. M. Embryonic Stem Cell Lines Derived from Human Blastocysts. Science, 1998, 282, 1145-1147.
4. Boheler, K. R., Czyz, J., Tweedie, D., Yang, H. T., Anisimov, S. V. and Wobus, A. M. Differentiation of Pluripotent Embryonic Stem Cells into Cardiomyocytes. Circ Res, 2002, 91, 189-201.
5. Gepstein, L. Derivation and Potential Applications of Human Embryonic Stem Cells. Circ.Res., 2002, 91, 866-876.
6. Kehat, I. and Gepstein, L. Human Embryonic Stem Cells for Myocardial Regeneration. Heart Fail.Rev., 2003, 8, 229-236.
7. Wobus, A. M. and Boheler, K. R. Embryonic Stem Cells: Prospects for Developmental Biology and Cell Therapy. Physiol Rev, 2005, 85, 635-678.
8. McBurney, M. W. and Rogers, B. J. Isolation of Male Embryonal Carcinoma Cells and Their Chromosome Replication Patterns. Developmental Biology, 1982, 89, 503-508.
9. Shamblott, M. J., Axelman, J., Wang, S., Bugg, E. M., Littlefield, J. W., Donovan, P. J., Blumenthal, P. D., Huggins, G. R. and Gearhart, J. D. Derivation of Pluripotent Stem Cells from Cultured Human Primordial Germ Cells. Proc Natl Acad Sci U S A, 1998, 95, 13726-13731.
10. Andrews, P. W. Teratocarcinomas and Human Embryology: Pluripotent Human Ec Cell Lines. Review Article. Apmis, 1998, 106, 158-167; discussion 167-158.
11. Przyborski, S. A., Christie, V. B., Hayman, M. W., Stewart, R. and Horrocks, G. M. Human Embryonal Carcinoma Stem Cells: Models of Embryonic Development in Humans. Stem Cells Dev, 2004, 13, 400-408.
12. Kehat, I., Gepstein, A., Spira, A., Itskovitz-Eldor, J. and Gepstein, L. High-Resolution Electrophysiological Assessment of Human Embryonic Stem Cell-Derived Cardiomyocytes: A Novel in Vitro Model for the Study of Conduction. Circ Res, 2002, 91, 659-661.
13. Xu, C., Police, S., Rao, N. and Carpenter, M. K. Characterization and Enrichment of Cardiomyocytes Derived from Human Embryonic Stem Cells. Circ Res, 2002, 91, 501-508.
14. He, J. Q., Ma, Y., Lee, Y., Thomson, J. A. and Kamp, T. J. Human Embryonic Stem Cells Develop into Multiple Types of Cardiac Myocytes: Action Potential Characterization. Circ Res, 2003, 93, 32-39.
15. 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. and Tertoolen, L. Differentiation of Human Embryonic Stem Cells to Cardiomyocytes: Role of Coculture with Visceral Endoderm-Like Cells. Circulation, 2003, 107, 2733-2740.
16. Schuldiner, M., Yanuka, O., Itskovitz-Eldor, J., Melton, D. A. and Benvenisty, N. Effects of Eight Growth Factors on the Differentiation of Cells Derived from Human Embryonic Stem Cells. Proc Natl Acad Sci U S A, 2000, 97, 11307-11312.
17. Kehat, I., Kenyagin-Karsenti, D., Snir, M., Segev, H., Amit, M., Gepstein, A., Livne, E., Binah, O., Itskovitz-Eldor, J. and Gepstein, L. Human Embryonic Stem Cells Can Differentiate into Myocytes with Structural and Functional Properties of Cardiomyocytes. J Clin Invest, 2001, 108, 407-414.
18. Itskovitz-Eldor, J., Schuldiner, M., Karsenti, D., Eden, A., Yanuka, O., Amit, M., Soreq, H. and Benvenisty, N. Differentiation of Human Embryonic Stem Cells into Embryoid Bodies Compromising the Three Embryonic Germ Layers. Mol Med, 2000, 6, 88-95.
19. Shamblott, M. J., Axelman, J., Littlefield, J. W., Blumenthal, P. D., Huggins, G. R., Cui, Y., Cheng, L. and Gearhart, J. D. Human Embryonic Germ Cell Derivatives Express a Broad Range of Developmentally Distinct Markers and Proliferate Extensively in Vitro. Proc Natl Acad Sci U S A, 2001, 98, 113-118.
20. Wei, G. and Mahowald, A. P. The Germline: Familiar and Newly Uncovered Properties. Annu Rev Genet, 1994, 28, 309-324.
21. Morgan, H. D., Santos, F., Green, K., Dean, W. and Reik, W. Epigenetic Reprogramming in Mammals. Hum Mol Genet, 2005, 14 Spec No 1, R47-58.
22. Soonpaa, M. H. and Field, L. J. Survey of Studies Examining Mammalian Cardiomyocyte DNA Synthesis. Circ Res, 1998, 83, 15-26.
23. Koh, G. Y., Soonpaa, M. H., Klug, M. G. and Field, L. J. Strategies for Myocardial Repair. J Interv Cardiol, 1995, 8, 387-393.
24. Soonpaa, M. H., Daud, A. I., Koh, G. Y., Klug, M. G., Kim, K. K., Wang, H. and Field, L. J. Potential Approaches for Myocardial Regeneration. Ann N Y Acad Sci, 1995, 752, 446-454.
25. Gage, F. H. Cell Therapy. Nature, 1998, 392, 18-24.
26. Murry, C. E., Wiseman, R. W., Schwartz, S. M. and Hauschka, S. D. Skeletal Myoblast Transplantation for Repair of Myocardial Necrosis. J Clin Invest, 1996, 98, 2512-2523.
27. Taylor, D. A., Atkins, B. Z., Hungspreugs, P., Jones, T. R., Reedy, M. C., Hutcheson, K. A., Glower, D. D. and Kraus, W. E. Regenerating Functional Myocardium: Improved Performance after Skeletal Myoblast Transplantation. Nat Med, 1998, 4, 929-933.
28. Koh, G. Y., Klug, M. G., Soonpaa, M. H. and Field, L. J. Differentiation and Long-Term Survival of C2c12 Myoblast Grafts in Heart. J Clin Invest, 1993, 92, 1548-1554.
29. Menasche, P., Hagege, A. A., Scorsin, M., Pouzet, B., Desnos, M., Duboc, D., Schwartz, K., Vilquin, J. T. and Marolleau, J. P. Myoblast Transplantation for Heart Failure. Lancet, 2001, 357, 279-280.
30. 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. and Duboc, D. Autologous Skeletal Myoblast Transplantation for Severe Postinfarction Left Ventricular Dysfunction. J. Am. Coll. Cardiol., 2003, 41, 1078-1083.
31. Orlic, D., Kajstura, J., Chimenti, S., Bodine, D. M., Leri, A. and Anversa, P. Transplanted Adult Bone Marrow Cells Repair Myocardial Infarcts in Mice. Ann N Y Acad Sci, 2001, 938, 221-229; discussion 229-230.
32. Orlic, D., Kajstura, J., Chimenti, S., Bodine, D. M., Leri, A. and Anversa, P. Bone Marrow Stem Cells Regenerate Infarcted Myocardium. Pediatr Transplant, 2003, 7 Suppl 3, 86-88.
33. Orlic, D., Kajstura, J., Chimenti, S., Limana, F., Jakoniuk, I., Quaini, F., Nadal-Ginard, B., Bodine, D. M., Leri, A. and Anversa, P. Mobilized Bone Marrow Cells Repair the Infarcted Heart, Improving Function and Survival. Proc Natl Acad Sci U S A, 2001, 98, 10344-10349.
34. Terada, N., Hamazaki, T., Oka, M., Hoki, M., Mastalerz, D. M., Nakano, Y., Meyer, E. M., Morel, L., Petersen, B. E. and Scott, E. W. Bone Marrow Cells Adopt the Phenotype of Other Cells by Spontaneous Cell Fusion. Nature, 2002, 416, 542-545.
35. Ying, Q. L., Nichols, J., Evans, E. P. and Smith, A. G. Changing Potency by Spontaneous Fusion. Nature, 2002, 416, 545-548.
36. ORLIC, D. Adult Bone Marrow Stem Cells Regenerate Myocardium in Ischemic Heart Disease. Ann NY Acad Sci, 2003, 996, 152-157.
37. Jiang, Y., Jahagirdar, B. N., Reinhardt, R. L., Schwartz, R. E., Keene, C. D., Ortiz-Gonzalez, X. R., Reyes, M., Lenvik, T., Lund, T., Blackstad, M., Du, J., Aldrich, S., Lisberg, A., Low, W. C., Largaespada, D. A. and Verfaillie, C. M. Pluripotency of Mesenchymal Stem Cells Derived from Adult Marrow. Nature, 2002, 418, 41-49.
38. Verfaillie, C. M. Adult Stem Cells: Assessing the Case for Pluripotency. Trends Cell Biol, 2002, 12, 502-508.
39. Balsam, L. B., Wagers, A. J., Christensen, J. L., Kofidis, T., Weissman, I. L. and Robbins, R. C. Haematopoietic Stem Cells Adopt Mature Haematopoietic Fates in Ischaemic Myocardium. Nature, 2004, 428, 668-673.
40. Murry, C. E., Soonpaa, M. H., Reinecke, H., Nakajima, H., Nakajima, H. O., Rubart, M., Pasumarthi, K. B., Virag, J. I., Bartelmez, S. H., Poppa, V., Bradford, G., Dowell, J. D., Williams, D. A. and Field, L. J. Haematopoietic Stem Cells Do Not Transdifferentiate into Cardiac Myocytes in Myocardial Infarcts. Nature, 2004, 428, 664-668.
41. Boheler, K. R. and Fiszman, M. Y. Can Exogenous Stem Cells Be Used in Transplantation? Cells Tissues Organs, 1999, 165, 237-245.
42. Wobus, A. M., Wallukat, G. and Hescheler, J. Pluripotent Mouse Embryonic Stem Cells Are Able to Differentiate into Cardiomyocytes Expressing Chronotropic Responses to Adrenergic and Cholinergic Agents and Ca2+ Channel Blockers. Differentiation, 1991, 48, 173-182.
43. Wobus, A. M., Kleppisch, T., Maltsev, V. and Hescheler, J. Cardiomyocyte-Like Cells Differentiated in Vitro from Embryonic Carcinoma Cells P19 Are Characterized by Functional Expression of Adrenoceptors and Ca2+ Channels. In Vitro Cell Dev Biol Anim, 1994, 30A, 425-434.
44. Wobus, A. M., Rohwedel, J., Maltsev, V. and Hescheler, J. Development of Cardiomyocytes Expressing Cardiac-Specific Genes, Action Potentials, and Ionic Channels During Embryonic Stem Cell-Derived Cardiogenesis. Ann N Y Acad Sci, 1995, 752, 460-469.
45. Wobus, A. M., Kaomei, G., Shan, J., Wellner, M. C., Rohwedel, J., Ji, G., Fleischmann, B., Katus, H. A., Hescheler, J. and Franz, W. M. Retinoic Acid Accelerates Embryonic Stem Cell-Derived Cardiac Differentiation and Enhances Development of Ventricular Cardiomyocytes. J Mol Cell Cardiol, 1997, 29, 1525-1539.
46. Czyz, J. and Wobus, A. Embryonic Stem Cell Differentiation: The Role of Extracellular Factors. Differentiation, 2001, 68, 167-174.
47. Wobus, A. M., Guan, K., Yang, H. T. and Boheler, K. R. Embryonic Stem Cells as a Model to Study Cardiac, Skeletal Muscle, and Vascular Smooth Muscle Cell Differentiation. Methods Mol Biol, 2002, 185, 127-156.
48. Westfall, M. V., Pasyk, K. A., Yule, D. I., Samuelson, L. C. and Metzger, J. M. Ultrastructure and Cell-Cell Coupling of Cardiac Myocytes Differentiating in Embryonic Stem Cell Cultures. Cell Motil Cytoskeleton, 1997, 36, 43-54.
49. Metzger, J. M., Samuelson, L. C., Rust, E. M. and Westfall, M. V. Embryonic Stem Cell Cardiogenesis: Applications for Cardiovascular Research. Trends in Cardiovascular Medicine, 1997, 7, 63-68.
50. Hescheler, J., Fleischmann, B. K., Lentini, S., Maltsev, V. A., Rohwedel, J., Wobus, A. M. and Addicks, K. Embryonic Stem Cells: A Model to Study Structural and Functional Properties in Cardiomyogenesis. Cardiovasc Res, 1997, 36, 149-162.
51. Liberatore, C. M., Searcy-Schrick, R. D., Vincent, E. B. and Yutzey, K. E. Nkx-2.5 Gene Induction in Mice Is Mediated by a Smad Consensus Regulatory Region. Dev Biol, 2002, 244, 243-256.
52. Lien, C. L., McAnally, J., Richardson, J. A. and Olson, E. N. Cardiac-Specific Activity of an Nkx2-5 Enhancer Requires an Evolutionarily Conserved Smad Binding Site. Dev. Biol., 2002, 244, 257-266.
53. Brand, T. Heart Development: Molecular Insights into Cardiac Specification and Early Morphogenesis. Dev.Biol., 2003, 258, 1-19.
54. Schultheiss, T. M., Burch, J. B. and Lassar, A. B. A Role for Bone Morphogenetic Proteins in the Induction of Cardiac Myogenesis. Genes Dev., 1997, 11, 451-462.
55. Andree, B., Duprez, D., Vorbusch, B., Arnold, H. H. and Brand, T. Bmp-2 Induces Ectopic Expression of Cardiac Lineage Markers and Interferes with Somite Formation in Chicken Embryos. Mech Dev, 1998, 70, 119-131.
56. Schlange, T., Andree, B., Arnold, H. H. and Brand, T. Bmp2 Is Required for Early Heart Development During a Distinct Time Period. Mech Dev, 2000, 91, 259-270.
57. Behfar, A., Zingman, L. V., Hodgson, D. M., Rauzier, J. M., Kane, G. C., Terzic, A. and Puceat, M. Stem Cell Differentiation Requires a Paracrine Pathway in the Heart. Faseb J, 2002, 16, 1558-1566.
58. Johansson, B. M. and Wiles, M. V. Evidence for Involvement of Activin a and Bone Morphogenetic Protein 4 in Mammalian Mesoderm and Hematopoietic Development. Mol Cell Biol, 1995, 15, 141-151.
59. Zaffran, S. and Frasch, M. Early Signals in Cardiac Development. Circ Res, 2002, 91, 457-469.
60. Gaussin, V., Van de Putte, T., Mishina, Y., Hanks, M. C., Zwijsen, A., Huylebroeck, D., Bebringer, R. R. and Schneider, M. D. Endocardial Cushion and Myocardial Defects after Cardiac Myocyte-Specific Conditional Deletion of the Bone Morphogenetic Protein Receptor Alk3. Proc Natl Acad Sci U S A, 2002, 99, 2878-2883.
61. Schneider, M. D., Gaussin, V. and Lyons, K. M. Tempting Fate: Bmp Signals for Cardiac Morphogenesis. Cytokine Growth Factor Rev, 2003, 14, 1-4.
62. Olson, E. N. and Schneider, M. D. Sizing up the Heart: Development Redux in Disease. Genes Dev., 2003, 17, 1937-1956.
63. Schneider, V. A. and Mercola, M. Wnt Antagonism Initiates Cardiogenesis in Xenopus Laevis. Genes Dev., 2001, 15, 304-315.
64. Lickert, H., Kutsch, S., Kanzler, B., Tamai, Y., Taketo, M. M. and Kemler, R. Formation of Multiple Hearts in Mice Following Deletion of Beta-Catenin in the Embryonic Endoderm. Dev. Cell, 2002, 3, 171-181.
65. Reya, T., Duncan, A. W., Ailles, L., Domen, J., Scherer, D. C., Willert, K., Hintz, L., Nusse, R. and Weissman, I. L. A Role for Wnt Signalling in Self-Renewal of Haematopoietic Stem Cells. Nature, 2003, 423, 409-414.
66. Willert, K., Brown, J. D., Danenberg, E., Duncan, A. W., Weissman, I. L., Reya, T., Yates, J. R., III and Nusse, R. Wnt Proteins Are Lipid-Modified and Can Act as Stern Cell Growth Factors. Nature, 2003, 423, 448-452.
67. Nakamura, T., Sano, M., Songyang, Z. and Schneider, M. D. A Wnt- and Beta -Catenin-Dependent Pathway for Mammalian Cardiac Myogenesis. Proc Natl Acad Sci U S A, 2003, 100, 5834-5839.
68. Ventura, C., Zinellu, E., Maninchedda, E. and Maioli, M. Dynorphin B Is an Agonist of Nuclear Opioid Receptors Coupling Nuclear Protein Kinase C Activation to the Transcription of Cardiogenic Genes in Gtrl Embryonic Stem Cells. Circ Res, 2003, 92, 623-629.
69. Ventura, C., Zinellu, E., Maninchedda, E., Fadda, M. and Maioli, M. Protein Kinase C Signaling Transduces Endorphin-Primed Cardiogenesis in Gtrl Embryonic Stem Cells. Circ Res, 2003, 92, 617-622.
70. Papadimou, E., Menard, C., Grey, C. and Puceat, M. Interplay between the Retinoblastoma Protein and Lek1 Specifies Stem Cells toward the Cardiac Lineage. Embo J, 2005, 24, 1750-1761.
71. Hidaka, K., Lee, J. K., Kim, H. S., Ihm, C. H., Iio, A., Ogawa, M., Nishikawa, S., Kodama, I. and Mrisaki, T. Chamber-Specific Differentiation of Nkx2.5-Positive Cardiac Precursor Cells from Murine Embryonic Stem Cells. Faseb J, 2003, 17, 740-742.
72. Takahashi, T., Lord, B., Schulze, P. C., Fryer, R. M., Sarang, S. S., Gullans, S. R. and Lee, R. T. Ascorbic Acid Enhances Differentiation of Embryonic Stem Cells into Cardiac Myocytes. Circulation, 2003, 107, 1912-1916.
73. Wu, X., Ding, S., Ding, Q., Gray, N. S. and Schultz, P. G. Small Molecules That Induce Cardiomyogenesis in Embryonic Stem Cells. J. Am. Chem. Soc., 2004, 126, 1590- 1591.
74. Klug, M. G., Soonpaa, M. H., Koh, G. Y. and Field, L. I. Genetically Selected Cardiomyocytes from Differentiating Embronic Stem Cells Form Stable Intracardiac Grafts. J.Clin.Invest, 1996, 98, 216-224.
75. Moore, J. C., van Laake, L. W., Braam, S. R., Xue, T., Tsang, S. Y., Ward, D., Passier, R., Tertoolen, L. L., Li, R. A. and Mummery, C. L. Human Embryonic Stem Cells: Genetic Manipulation on the Way to Cardiac Cell Therapies. Reprod Toxicol, 2005, 20, 377-391.
76. Odorico, J. S., Kaufman, D. S. and Thomson, J. A. Multilineage Differentiation from Human Embryonic Stem Cell Lines. Stem Cells, 2001, 19, 193-204.
77. Reppel, M., Boettinger, C. and Hescheler, J. Beta-Adrenergic and Muscarinic Modulation of Human Embryonic Stem Cell-Derived Cardiomyocytes. Cell Physiol Biochem, 2004, 14, 187-196.
78. Snir, M., Kehat, I., Gepstein, A., Coleman, R., Itskovitz-Eldor, J., Livne, E. and Gepstein, L. Assessment of the Ultrastructural and Proliferative Properties of Human Embryonic Stem Cell-Derived Cardiomyocytes. Am. J. Physiol Heart Circ. Physiol, 2003, 285, H2355-H2363.
79. Braude, P., Bolton, V. and Moore, S. Human Gene Expression First Occurs between the Four- and Eight-Cell Stages of Preimplantation Development. Nature, 1988, 332, 459-461.
80. Luckett, W. P. Origin and Differentiation of the Yolk Sac and Extraembryonic Mesoderm in Presomite Human and Rhesus Monkey Embryos. Am J Anat, 1978, 152, 59-97.
81. Thomson, J. A. and Odorico, J. S. Human Embryonic Stem Cell and Embryonic Germ Cell Lines. Trends Biotechnol, 2000, 18, 53-57.
82. Eriksson, H. Heart Failure: A Growing Public Health Problem. J Intern Med, 1995, 237, 135-141.
83. Lanza, R. P., Cibelli, J. B. and West, M. D. Human Therapeutic Cloning. Nat Med, 1999, 5, 975-977.
84. Lanza, R. P., Cibelli, J. B. and West, M. D. Prospects for the Use of Nuclear Transfer in Human Transplantation. Nat Biotechnol, 1999, 17, 1171-1174.
85. Hwang, W. S., Ryu, Y. J., Park, J. H., Park, E. S., Lee, E. G., Koo, J. M., Jeon, H. Y., Lee, B. C., Kang, S. K., Kim, S. J., Ahn C., Hwang, J. H., Park, K. Y., Cibelli, J. B. and Moon, S. Y. Evidence of a Pluripotent Human Embryonic Stem Cell Line Derived from a Cloned Blastocyst. Science, 2004, 303, 1669-1674.
86. Hwang, W. S., Roh, S. I., Lee, B. C., Kang, S. K., Kwon, D. K., Kim, S., Kim, S. J., Park, S. W., Kwon, H. S., Lee, C. K., Lee, J. B., Kim, J. M., Ahn, C., Paek, S. H., Chang, S. S., Koo, J. J., Yoon, H. S., Hwang, J. H., Hwang, Y. Y., Park, Y. S., Oh, S. K., Kim, H. S., Park, J. H., Moon, S. Y. and Schatten, G. Patient-Specific Embryonic Stem Cells Derived from Human Scnt Blastocysts. Science, 2005, 308, 1777-1783.
87. Miake, J., Marban, E. and Nuss, H. B. Gene Therapy: Biological Pacemaker Created by Gene Transfer. Nature, 2002, 419, 132-133.
88. Xue, T., Chan, C., Henrikson, C., Sang, D., Marban, E. and Li, R. Lentivirus-Mediated Genetic Manipulations of Human Embryonic Stem Cells and Their Cardiac Derivatives. Circulation, 2003, 108:IV33,
89. Robinson, R. B. and Siegelbaum, S. A. Hyperpolarization-Activated Cation Currents: From Molecules to Physiological Function. Annu Rev Physiol, 2003, 65, 453-480.
90. Rubart, M., Pasumarthi, K. B., Nakajima, H., Soonpaa, M. H., Nakajima, H. O. and Field, L. J. Physiological Coupling of Donor and Host Cardiomyocytes after Cellular Transplantation. Circ Res, 2003, 92, 1217-1224.
91. Rosen, M. R., Robinson, R. B., Brink, P. and Cohen, I. S. Recreating the Biological Pacemaker. Anat Rec A Discov Mol Cell Evol Biol, 2004, 280, 1046-1052.
92. Xue, T. and Li, R. A. Circulation, 2005, 112, e82-83.
93. Robinson, R. B., Rosen, M. R., Brink, P. R. and Cohen, I. S. Circulation, 2005, 112, e82.
94. Boyett, M. R., Honjo, H. and Kodama, I. The Sinoatrial Node, a Heterogeneous Pacemaker Structure. Cardiovascular Research, 2000, 47, 658-687.
95. Maitra, A., Arking, D. E., Shivapurkar, N., Ikeda, M., Stastny, V., Kassauei, K., Sui, G., Cutler, D. J., Liu, Y., Brimble, S. N., Noaksson, K., Hyllner, J., Schulz, T. C., Zeng, X., Freed, W. J., Crook, J., Abraham, S., Colman, A., Sartipy, P., Matsui, S., Carpenter, M., Gazdar, A. F., Rao, M. and Chakravarti, A. Genomic Alterations in Cultured Human Embryonic Stem Cells. Nat Genet, 2005, 37, 1099-1103.
96. Xue, T., Cho, H.C., Akar, F.G., Tsang, S.-Y., Jones, S.P., Marban, E., Tomaselli, G.F., Li, RA. Functional integration of electrically active cardiac derivatives from genetically engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes. Circulation, 2005, 111, 11-20.
97. Bobeler, K.R., Wobus, A.M. Myocardial Aging and Embryonic Stem Cell Biology. Advances in Cell Aging and Gerontology. In Stem Cells: A Cellular Fountain of Youth? (Mattson MP, van Zant G, Eds) Elsevier Press. 2002, 141-177.