Stem Cell Reviews

, Volume 4, Issue 3, pp 217–225 | Cite as

The Therapeutic Potential of Embryonic and Adult Stem Cells for Skeletal Muscle Regeneration

  • Radbod Darabi
  • Filipe N. C. Santos
  • Rita C. R. Perlingeiro


Muscular dystrophy (MD) refers to a group of more than 30 genetically and clinically heterogeneous disorders, characterized by progressive weakness and degeneration of the skeletal muscles that control movement. To date, MD is still incurable but increasing evidence suggests that stem cells might represent a therapeutic option in the future. This review will outline recent progress in this field involving the use of adult and embryonic stem cells. We will discuss in further detail the nature of these cells and their distinct biological properties which lead to their unique advantages and disadvantages in regard to therapeutic application.


Embryonic stem cells Adult stem cells Pax3 Myogenesis Muscle regeneration Cell therapy Muscular dystrophy 


  1. 1.
    Emery, A. E. (2002). The muscular dystrophies. Lancet, 359, 687–695.PubMedCrossRefGoogle Scholar
  2. 2.
    Koenig, M., Hoffman, E. P., Bertelson, C. J., Monaco, A. P., Feener, C., & Kunkel, L. M. (1987). Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell, 50, 509–517.PubMedCrossRefGoogle Scholar
  3. 3.
    Hoffman, E. P., Brown, R. H. J., & Kunkel, L. M. (1987). Dystrophin: The protein product of the Duchenne muscular dystrophy locus. Cell, 51, 919–928.PubMedCrossRefGoogle Scholar
  4. 4.
    Brussee, V., Tardif, F., Roy, B., Goulet, M., Sebille, A., & Tremblay, J. P. (1999). Successful myoblast transplantation in fibrotic muscles: no increased impairment by the connective tissue. Transplantation, 67, 1618–1622.PubMedCrossRefGoogle Scholar
  5. 5.
    Gussoni, E., Blau, H. M., & Kunkel, L. M. (1997). The fate of individual myoblasts after transplantation into muscles of DMD patients. Nature Medicine, 3, 970–977.PubMedCrossRefGoogle Scholar
  6. 6.
    Partridge, T. A., Morgan, J. E., Coulton, G. R., Hoffman, E. P., & Kunkel, L. M. (1989). Conversion of mdx myofibers from dystrophin-negative to positive by injection of normal myoblasts. Nature, 337, 176–179.PubMedCrossRefGoogle Scholar
  7. 7.
    Qu, Z., Balkir, L., van Deutekom, J. C., Robbins, P. D., Pruchnic, R., & Huard, J. (1998). Development of approaches to improve cell survival in myoblast transfer therapy. Journal of Cell Biology, 142, 1267.Google Scholar
  8. 8.
    Mendell, J. R., Kissel, J. T., Amato, A. A., King, W., Signore, L., Prior, T. W., et al. (1995). Myoblast transfer in the treatment of Duchenne’s muscular dystrophy. New England Journal of Medicine, 333, 832–838.PubMedCrossRefGoogle Scholar
  9. 9.
    Partridge, T., Lu, Q. L., Morris, G., & Hoffman, E. (1998). Is myoblast transplantation effective? Nature Medicine, 4, 1208–1209.PubMedCrossRefGoogle Scholar
  10. 10.
    Tremblay, J. P., Malouin, F., Roy, R., Huard, J., Bouchard, J. P., Satoh, A., et al. (1993). Results of a triple blind clinical study of myoblast transplantations without immunosuppressive treatment in young boys with Duchenne muscular dystrophy. Cell Transplantation, 2, 99–112.PubMedGoogle Scholar
  11. 11.
    Vilquin, J. T. (2005). Myoblast transplantation: Clinical trials and perspectives. Acta Myologica, 24, 119–27.PubMedGoogle Scholar
  12. 12.
    Mauro, A. (1961). Satellite cells of skeletal muscle fibres. Journal of Biophysical and Biochemical Cytology, 9, 493–496.PubMedCrossRefGoogle Scholar
  13. 13.
    Cornelison, D. D., & Wold, B. J. (1997). Single-cell analysis of regulatory gene expression in quiescent and activated mouse skeletal muscle satellite cells. Developments in Biologicals, 191, 270–283.CrossRefGoogle Scholar
  14. 14.
    Sherwood I, R., Christensen, J. L., Weissman, I. L., & Wagers, A. J. (2004). Determinants of skeletal muscle contributions from circulating cells, bone marrow cells, and hematopoietic stem cells. Stem Cells, 22, 1292–304.PubMedCrossRefGoogle Scholar
  15. 15.
    Cornelison, D. D., Filla, M. S., Stanley, H. M., Rapraeger, A. C., & Olwin, B. B. (2001). Syndecan-3 and syndecan-4 specifically mark skeletal muscle satellite cells and are implicated in satellite cell maintenance and muscle regeneration. Developments in Biologicals, 239, 79–94.CrossRefGoogle Scholar
  16. 16.
    Oustanina, S., Hause, G., & Braun, T. (2004). Pax7 directs postnal renewal and propagation of myogenic satellite cells but not their specification. EMBO Journal, 23, 3430–3439.PubMedCrossRefGoogle Scholar
  17. 17.
    Seale, P., Sabourin, L. A., Girgis-Gabardo, A., Mansouri, A., Gruss, P., & Rudnicki, M. A. (2000). Pax7 is required for the specification of myogenic satellite cells. Cell, 102, 777–786.PubMedCrossRefGoogle Scholar
  18. 18.
    Zammit, P. S., Golding, J. P., Nagata, Y., Hudon, V., Partridge, T. A., & Beauchamp, J. R. (2004). Muscle satellite cells adopt divergent fates: a mechanism for self-renewal? Journal of Cell Biology, 166, 347–357.PubMedCrossRefGoogle Scholar
  19. 19.
    Halevy, O., Piestun, Y., Allouh, M. Z., Rosser, B. W., Rinkevich, Y., Reshef, R., et al. (2004). Pattern of Pax7 expression during myogenesis in the posthatch chicken establishes a model for satellite cell differentiation and renewal. Developmental Dynamics, 231, 489–502.PubMedCrossRefGoogle Scholar
  20. 20.
    Olguin, H. C., & Olwin, B. B. (2004). Pax-7 up-regulation inhibits myogenesis and cell cycle progression in satellite cells: a potential mechanism for self-renewal. Developments in Biologicals, 275, 375–388.CrossRefGoogle Scholar
  21. 21.
    Kuang, S., Kuroda, K., Le Grand, F., & Rudnicki, M. A. (2007). Asymmetric self-renewal and commitment of satellite stem cells in muscle. Cell, 129, 999–1010.PubMedCrossRefGoogle Scholar
  22. 22.
    Collins, C. A., Olsen, I., Zammit, P. S., Heslop, L., Petrie, A., Partridge, T. A., et al. (2005). Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell, 122, 289–301.PubMedCrossRefGoogle Scholar
  23. 23.
    Montarras, D., Morgan, J., Collins, C., Relaix, F., Zaffran, S., Cumano, A., et al. (2005). Direct isolation of satellite cells for skeletal muscle regeneration. Science, 309, 2064–2067.PubMedCrossRefGoogle Scholar
  24. 24.
    Sherwood, R. I., Christensen, J. L., Conboy, I. M., Conboy, M. J., Rando, T. A., Weissman, I. L., et al. (2004). Isolation of adult mouse myogenic progenitors: functional heterogeneity of cells within and engrafting skeletal muscle. Cell, 119, 543–54.PubMedCrossRefGoogle Scholar
  25. 25.
    van der Loo, J. C., & Ploemacher, R. E. (1995). Marrow- and spleen-seeding efficiencies of all murine hematopoietic stem cell subsets are decreased by preincubation with hematopoietic growth factors. Blood, 85, 2598–2606.PubMedGoogle Scholar
  26. 26.
    Traycoff, C. M., Cornetta, K., Yoder, M. C., Davidson, A., & Srour, E. F. (1996). Ex vivo expansion of murine hematopoietic progenitor cells generates classes of expanded cells possessing different levels of bone marrow repopulating potential. Experimental Hematology, 24, 299–306.PubMedGoogle Scholar
  27. 27.
    Guenechea, G., Segovia, J. C., Albella, B., Lamana, M., Ramírez, M., Regidor, C., Fernández, M. N., Bueren, J. A., et al. (1999). Delayed engraftment of nonobese diabetic/severe combined immunodeficient mice transplanted with ex vivo-expanded human CD34(+) cord blood cells. Blood, 93, 1097–1105.PubMedGoogle Scholar
  28. 28.
    Qu-Petersen, Z., Deasy, B., Jankowski, R., Ikezawa, M., Cummins, J., Pruchnic, R., et al. (2002). Identification of a novel population of muscle stem cells in mice: Potential for muscle regeneration. Journal of Cell Biology, 157, 851–864.PubMedCrossRefGoogle Scholar
  29. 29.
    Deasy, B. M., Jankowski, R. J., & Huard, J. (2001). Muscle-derived stem cells: Characterization and potential for cell-mediated therapy. Blood Cells, Molecules and Disease, 27, 924–933.CrossRefGoogle Scholar
  30. 30.
    Torrente, Y., Tremblay, J. P., Pisati, F., Belicchi, M., Rossi, B., Sironi, M., et al. (2001). Intraarterial injection of muscle-derived CD34(+)Sca-1(+) stem cells restores dystrophin in mdx mice. Journal of Cell Biology, 152, 335–348.PubMedCrossRefGoogle Scholar
  31. 31.
    Mueller, G. M., O’Day, T., Watchko, J. F., & Ontell, M. (2002). Effect of injecting primary myoblasts versus putative muscle-derived stem cells on mass and force generation in mdx mice. Human Gene Therapy, 13, 1081–1090.PubMedCrossRefGoogle Scholar
  32. 32.
    Goodell, M. A., Brose, K., Paradis, G., Conner, A. S., Mulligan, R. C., et al. (1996). Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. Journal of Experimental Medicine, 183, 1797–806.PubMedCrossRefGoogle Scholar
  33. 33.
    Goodell, M. A., Rosenzweig, M., Kim, H., Marks, D. F., DeMaria, M., & Paradis, G. (1997). Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nature Medicine, 3, 1337–1345.PubMedCrossRefGoogle Scholar
  34. 34.
    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, 239–243.PubMedCrossRefGoogle Scholar
  35. 35.
    Inowa, T., Hishikawa, K., Takeuchi, T., Kitamura, T., & Fujita, T. (2008). Isolation and potential existence of side population cells in adult human kidney. International Journal of Urology, 15, 272–274.PubMedCrossRefGoogle Scholar
  36. 36.
    Welm, B. E., Tepera, S. B., Venezia, T., Graubert, T. A., Rosen, J. M., & Goodell, M. A. (2002). Sca-1(pos) cells in the mouse mammary gland represent an enriched progenitor cell population. Developments in Biologicals, 245, 42–56.CrossRefGoogle Scholar
  37. 37.
    Martin, C. M., Meeson, A. P., Robertson, S. M., Hawke, T. J., Richardson, J. A., Bates, S., et al. (2004). Persistent expression of the ATP-binding cassette transporter, Abcg2, identifies cardiac SP cells in the developing and adult heart. Developments in Biologicals, 265, 262–75.CrossRefGoogle Scholar
  38. 38.
    Tsuchiya, A., Heike, T., Baba, S., Fujino, H., Umeda, K., Matsuda, Y., et al. (2007). Long-term culture of postnatal mouse hepatic stem/progenitor cells and their relative developmental hierarchy. Stem Cells, 25, 895–902.PubMedCrossRefGoogle Scholar
  39. 39.
    Gussoni, E., Soneoka, Y., Strickland, C. D., Buzney, E. A., Khan, M. K., Flint, A. F., et al. (1999). Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature, 401, 390–394.PubMedGoogle Scholar
  40. 40.
    Asakura, A., Seale, P., Girgis-Gabardo, A., & Rudnicki, M. A. (2002). Myogenic specification of side population cells in skeletal muscle. Journal of Cell Biology, 159, 123–134.PubMedCrossRefGoogle Scholar
  41. 41.
    Bachrach, E., Perez, A. L., Choi, Y. H., Illigens, B. M., Jun, S. J., del Nido, P., et al. (2006). Muscle engraftment of myogenic progenitor cells following intraarterial transplantation. Muscle Nerve, 34, 44–52.PubMedCrossRefGoogle Scholar
  42. 42.
    Ferrari, G., Cusella-De Angelis, G., Coletta, M., Paolucci, E., Stornaiuolo, A., Cossu, G., et al. (1998). Muscle regeneration by bone marrow-derived myogenic progenitors. Science, 279, 1528–1530.PubMedCrossRefGoogle Scholar
  43. 43.
    Bittner, R. E., Schofer, C., Weipoltshammer, K., Ivanova, S., Streubel, B., Hauser, E., et al. (1999). Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice. Anatomy and Embryology (Berl), 199, 391–396.CrossRefGoogle Scholar
  44. 44.
    Fukada, S., Miyagoe-Suzuki, Y., Tsukihara, H., Yuasa, K., Higuchi, S., Ono, S., et al. (2002). Muscle regeneration by reconstitution with bone marrow or fetal liver cells from green fluorescent protein-gene transgenic mice. Journal of Cell Science, 115, 1285–1293.PubMedGoogle Scholar
  45. 45.
    Ferrari, G., Stornaiuolo, A., & Mavilio, F. (2001). Failure to correct murine muscular dystrophy. Nature, 411, 1014–1015.PubMedCrossRefGoogle Scholar
  46. 46.
    Camargo, F. D., Green, R., Capetanaki, Y., Jackson, K. A., & Goodell, M. A. (2003). Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates. Nature Medicine, 9, 1520–1527.PubMedCrossRefGoogle Scholar
  47. 47.
    Saito, T., Dennis, J. E., Lennon, D. P., Young, R. G., & Caplan, A. I. (1995). Myogenic expression of mesenchymal stem cells within myotubes of mdx mice in vitro and in vivo. Tissue Engineering, 1, 327–243.CrossRefPubMedGoogle Scholar
  48. 48.
    Rodriguez, A. M., Pisani, D., Dechesne, C. A., Turc-Carel, C., Kurzenne, J. Y., Wdziekonski, B., et al. (2005). Transplantation of a multipotent cell population from human adipose tissue induces dystrophin expression in the immunocompetent mdx mouse. Journal of Experimental Medicine, 201, 1397–1405.PubMedCrossRefGoogle Scholar
  49. 49.
    De Bari, C., Dell’Accio, F., Vandenabeele, F., Vermeesch, J. R., Raymackers, J. M., & Luyten, F. P. (2003). Skeletal muscle repair by adult human mesenchymal stem cells from synovial membrane. Journal of Cell Biology, 60, 909–918.CrossRefGoogle Scholar
  50. 50.
    Dezawa, M., Ishikawa, H., Itokazu, Y., Yoshihara, T., Hoshino, M., Takeda, S., et al. (2005). Bone marrow stromal cells generate muscle cells and repair muscle degeneration. Science, 309, 314–317.PubMedCrossRefGoogle Scholar
  51. 51.
    Gang, E. J., Bosnakovski, D., Simsek, T., To, K., Perlingeiro, R. C. R. (2008). Pax3 activation promotes the differentiation of mesenchymal stem cells toward the myogenic lineage. Experimental Cell Research, doi:10.1016/j.yexcr.2008.02.016.
  52. 52.
    Yin, A. H., Miraglia, S., Zanjani, E. D., Almeida-Porada, G., Ogawa, M., Leary, A. G., et al. (1997). AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood, 90(12), 5002–5012, Dec 15.PubMedGoogle Scholar
  53. 53.
    de Wynter, E. A., Buck, D., Hart, C., Heywood, R., Coutinho, L. H., & Clayton, A. (1998). CD34+AC133+cells isolated from cord blood are highly enriched in long-term culture-initiating cells, NOD/SCID-repopulating cells and dendritic cell progenitors. Stem Cells, 16, 387–396.PubMedCrossRefGoogle Scholar
  54. 54.
    Peichev, M. N. A., Pereira, D., Zhu, Z., Lane, W. J., Williams, M., Oz, M. C., et al. (2000). Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood, 95, 952–958.PubMedGoogle Scholar
  55. 55.
    Salven, P., Mustjoki, S., Alitalo, R., Alitalo, K., & Rafii, S. (2003). VEGFR-3 and CD133 identify a population of CD34+lymphatic/vascular endothelial precursor cells. Blood, 101, 168–172.PubMedCrossRefGoogle Scholar
  56. 56.
    Sawamoto, K., Nakao, N., Kakishita, K., Ogawa, Y., Toyama, Y., Yamamoto, A., et al. (2001). Generation of dopaminergic neurons in the adult brain from mesencephalic precursor cells labeled with a nestin-GFP transgene. Journal of Neuroscience, 21, 3895–3903.PubMedGoogle Scholar
  57. 57.
    Torrente, Y., Belicchi, M., Sampaolesi, M., Pisati, F., Meregalli, M., D’Antona, G., et al. (2004). Human circulating AC133(+) stem cells restore dystrophin expression and ameliorate function in dystrophic skeletal muscle. Journal of Clinical Investigation, 114, 182–195.PubMedGoogle Scholar
  58. 58.
    Torrente, Y., Belicchi, M., Marchesi, C., Dantona, G., Cogiamanian, F., Pisati, F., et al. (2007). Autologous transplantation of muscle-derived CD133 + stem cells in Duchenne muscle patients. Cell Transplant, 16, 563–577.PubMedGoogle Scholar
  59. 59.
    Benchaouir, R., Meregalli, M., Farini, A., D’Antona, G., Belicchi, M., Goyenvalle, A., et al. (2007). Restoration of human dystrophin following transplantation of exon-skipping-engineered DMD patient stem cells into dystrophic mice. Cell Stem Cell, 1, 646–657.PubMedCrossRefGoogle Scholar
  60. 60.
    De Angelis, L., Berghella, L., Coletta, M., Lattanzi, L., Zanchi, M., Cusella-De Angelis, M. G., et al. (1999). Skeletal myogenic progenitors originating from embryonic dorsal aorta coexpress endothelial and myogenic markers and contribute to postnatal muscle growth and regeneration. Journal of Cell Biology, 147, 869–878.PubMedCrossRefGoogle Scholar
  61. 61.
    Minasi, M. G., Riminucci, M., De Angelis, L., Borello, U., Berarducci, B., Innocenzi, A., et al. (2002). The meso-angioblast: a multipotent, self-renewing cell that originates from the dorsal aorta and differentiates into most mesodermal tissues. Development, 129, 2773–2783.PubMedGoogle Scholar
  62. 62.
    Sampaolesi, M., Blot, S., D’Antona, G., Granger, N., Tonlorenzi, R., Innocenzi, A., et al. (2006). Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs. Nature, 444, 574–579.PubMedCrossRefGoogle Scholar
  63. 63.
    Dellavalle, A., Sampaolesi, M., Tonlorenzi, R., Tagliafico, E., Sacchetti, B., Perani, L., et al. (2007). Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nature of Cell Biology, 9, 255–267.CrossRefGoogle Scholar
  64. 64.
    Sampaolesi, M., Torrente, Y., Innocenzi, A., Tonlorenzi, R., D’Antona, G., Pellegrino, M. A., et al. (2003). Cell therapy of alpha-sarcoglycan null dystrophic mice through intra-arterial delivery of mesoangioblasts. Science, 301, 487–492.PubMedCrossRefGoogle Scholar
  65. 65.
    Mintz, B., & Illmensee, K. (1975). Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proceedings of the National Academy of Sciences of the United States of America, 72, 3585–35859.PubMedCrossRefGoogle Scholar
  66. 66.
    Evans, M. J., & Kaufman, M. H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature, 292, 154–156.PubMedCrossRefGoogle Scholar
  67. 67.
    Martin, G. R. (1981). Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proceedings of the National Academy of Sciences of the United States of America, 78, 7634–7638.PubMedCrossRefGoogle Scholar
  68. 68.
    Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282, 1145–1147.PubMedCrossRefGoogle Scholar
  69. 69.
    Bradley, A., Evans, M., Kaufman, M. H., & Robertson, E. (1984). Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines. Nature, 309, 255–256.PubMedCrossRefGoogle Scholar
  70. 70.
    Martin, G. R., & Evans, M. J. (1975). Differentiation of clonal lines of teratocarcinoma cells: formation of embryoid bodies in vitro. Proceedings of the National Academy of Sciences of the United States of America, 72, 1441–1445.PubMedCrossRefGoogle Scholar
  71. 71.
    Martin, G. R., Wiley, L. M., & Damjanov, I. (1977). The development of cystic embryoid bodies in vitro from clonal teratocarcinoma stem cells. Developments in Biologicals, 61, 230–244.CrossRefGoogle Scholar
  72. 72.
    Leahy, A., Xiong, J. W., Kuhnert, F., & Stuhlmann, H. (1999). Use of developmental marker genes to define temporal and spatial patterns of differentiation during embryoid body formation. Journal of Experimental Zoology, 284, 67–81.PubMedCrossRefGoogle Scholar
  73. 73.
    Rathjen, J., & Rathjen, P. D. (2001). Mouse ES cells: experimental exploitation of pluripotent differentiation potential. Current Opinion Genetics and Develeopmet, 11, 587–594.CrossRefGoogle Scholar
  74. 74.
    Perlingeiro, R. C., Kyba, M., & Daley, G. Q. (2001). Clonal analysis of differentiating embryonic stem cells reveals a hematopoietic progenitor with primitive erythroid and adult lymphoid-myeloid potential. Development, 128, 4597–4604.PubMedGoogle Scholar
  75. 75.
    Doetschman, T. C., Eistetter, H., Katz, M., Schmidt, W., & Kemler, R. (1985). The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. Journal of Embryology and Experimental Morphology, 87, 27–45.PubMedGoogle Scholar
  76. 76.
    Schmitt, R. M., Bruyns, E., & Snodgrass, H. R. (1991). Hematopoietic development of embryonic stem cells in vitro: cytokine and receptor gene expression. Genes and Development, 5, 728–740.PubMedCrossRefGoogle Scholar
  77. 77.
    Wiles, M. V., & Keller, G. (1991). Multiple hematopoietic lineages develop from embryonic stem (ES) cells in culture. Development, 111, 259–267.PubMedGoogle Scholar
  78. 78.
    Kyba, M., Perlingeiro, R. C., & Daley, G. Q. (2002). HoxB4 confers definitive lymphoid-myeloid engraftment potential on embryonic stem cell and yolk sac hematopoietic progenitors. Cell, 109, 29–37.PubMedCrossRefGoogle Scholar
  79. 79.
    Soria, B., Roche, E., Berná, G., León-Quinto, T., Reig, J. A., & Martín, F. (2000). Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes, 49, 157–162.PubMedCrossRefGoogle Scholar
  80. 80.
    Lumelsky, N., Blondel, O., Laeng, P., Velasco, I., Ravin, R., & McKay, R. (2001). Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science, 292, 1389–1394.PubMedCrossRefGoogle Scholar
  81. 81.
    Assady, S., Maor, G., Amit, M., Itskovitz-Eldor, J., Skorecki, K. L., & Tzukerman, M. (2001). Insulin production by human embryonic stem cells. Diabetes, 50, 1691–1697.PubMedCrossRefGoogle Scholar
  82. 82.
    Hamazaki, T., Iiboshi, Y., Oka, M., Papst, P. J., Meacham, A. M., Zon, L. I., Terada, N., et al. (2001). Hepatic maturation in differentiating embryonic stem cells in vitro. FEBS Letter, 497, 15–19.CrossRefGoogle Scholar
  83. 83.
    Rambhatla, L., Chiu, C. P., Kundu, P., Peng, Y., & Carpenter, M. K. (2003). Generation of hepatocyte-like cells from human embryonic stem cells. Cell Transplant, 12, 1–11.PubMedCrossRefGoogle Scholar
  84. 84.
    Zhang, S. C., Wernig, M., Duncan, I. D., Brüstle, O., & Thomson, J. A. (2001). In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nature Biotechnology, 19, 1129–1133.PubMedCrossRefGoogle Scholar
  85. 85.
    Bain, G., Kitchens, D., Yao, M., Huettner, J. E., & Gottlieb, D. I. (1996). Embryonic stem cells express neuronal properties in vitro. Developments in Biologicals, 168, 342–357.CrossRefGoogle Scholar
  86. 86.
    Hübner, K., Fuhrmann, G., Christenson, L. K., Kehler, J., Reinbold, R., De La Fuente, R., Wood, J., Strauss, J. Fr., et al. (2003). Derivation of oocytes from mouse embryonic stem cells. Science, 300, 1251–1256.PubMedCrossRefGoogle Scholar
  87. 87.
    Geijsen, N., Horoschak, M., Kim, K., Gribnau, J., Eggan, K., & Daley, G. Q. (2004). Derivation of embryonic germ cells and male gametes from embryonic stem cells. Nature, 427, 148–154.PubMedCrossRefGoogle Scholar
  88. 88.
    Toyooka, Y. T. N., Akasu, R., & Noce, T. (2003). Embryonic stem cells can form germ cells in vitro. Proceedings of the National Academy of Sciences of the United States of America, 100, 11457–11462.PubMedCrossRefGoogle Scholar
  89. 89.
    Klug, M. G., Soonpaa, M. H., Koh, G. Y., & Field, L. J. (1996). Genetically selected cardiomyocytes from differentiating embryonic stem cells form stable intracardiac grafts. Journal of Clinical Invest, 98, 216–224.CrossRefGoogle Scholar
  90. 90.
    Müller, M., Fleischmann, B. K., Selbert, S., Ji, G. J., Endl, E., Middeler, G., et al. (2000). Selection of ventricular-like cardiomyocytes from ES cells in vitro. FASEB Journal, 14, 2540–2548.PubMedCrossRefGoogle Scholar
  91. 91.
    He, J. Q., Ma, Y., Lee, Y., Thomson, J. A., & Kamp, T. J. (2003). Human embryonic stem cells develop into multiple types of cardiac myocytes: action potential characterization. Circulation Research, 93, 32–39.PubMedCrossRefGoogle Scholar
  92. 92.
    Drab, M., Haller, H., Bychkov, R., Erdmann, B., Lindschau, C., Haase, H., et al. (1997). From totipotent embryonic stem cells to spontaneously contracting smooth muscle cells: a retinoic acid and db-cAMP in vitro differentiation model. FASEB Journal, 11, 905–915.PubMedGoogle Scholar
  93. 93.
    Rohwedel, J., Maltsev, V., Bober, E., Arnold, H. H., Hescheler, J., & Wobus, A. M. (1994). Muscle cell differentiation of embryonic stem cells reflects myogenesis in vivo: developmentally regulated expression of myogenic determination genes and functional expression of ionic currents. Developments in Biologicals, 164, 87–101.CrossRefGoogle Scholar
  94. 94.
    Barberi, T., Bradbury, M., Dincer, Z., Panagiotakos, G., Socci, N. D., & Studer, L. (2007). Derivation of engraftable skeletal myoblasts from human embryonic stem cells. Nature Medicine, 13, 642–648.PubMedCrossRefGoogle Scholar
  95. 95.
    Bhagavati, S., & Xu, W. (2005). Generation of skeletal muscle from transplanted embryonic stem cells in dystrophic mice. Biochemical and Biophysical Research Communicaitons, 333, 644–649.CrossRefGoogle Scholar
  96. 96.
    Darabi, R., Gehlbach, K., Bachoo, R. M., Kamath, S., Osawa, M., Kamm, K. E., et al. (2008). Functional skeletal muscle regeneration from differentiating embryonic stem cells. Nature Medicine, 14, 134–143.PubMedCrossRefGoogle Scholar
  97. 97.
    Ridgeway, A. G., & Skerjanc, I. S. (2001). Pax3 is essential for skeletal myogenesis and the expression of Six1 and Eya2. Journal of Biology Chemicals, 276, 19033–19039.CrossRefGoogle Scholar
  98. 98.
    Mylona, E., Jones, K. A., Mills, S. T., & Pavlath, G. K. (2006). CD44 regulates myoblast migration and differentiation. Journal of Cell Physiology, 209, 314–321.CrossRefGoogle Scholar
  99. 99.
    Prentice, D. A. (2006). Current science of regenerative medicine with stem cells. Journal of Investigative Medicine, 54, 33–37.PubMedCrossRefGoogle Scholar
  100. 100.
    Briggs, R., & King, T. J. (1952). Transplantation of Living Nuclei From Blastula Cells into Enucleated Frogs’ Eggs. Proceedings of the National Academy of Sciences of the United States of America, 38, 455–463.PubMedCrossRefGoogle Scholar
  101. 101.
    Gurdon, J. B., Elsdale, T. R., & Fischberg, M. (1958). Sexually mature individuals of Xenopus laevis from the transplantation of single somatic nuclei. Nature, 182, 64–65.PubMedCrossRefGoogle Scholar
  102. 102.
    Willadsen, S. M. (1986). Nuclear transplantation in sheep embryos. Nature, 320, 63–65.PubMedCrossRefGoogle Scholar
  103. 103.
    Prather, R. S., Barnes, F. L., Sims, M. M., Robl, J. M., Eyestone, W. H., & First, N. L. (1987). Nuclear transplantation in the bovine embryo: assessment of donor nuclei and recipient oocyte. Biology of Reproduction, 37, 859–866.PubMedCrossRefGoogle Scholar
  104. 104.
    Wilmut, I., Schnieke, A. E., McWhir, J., Kind, A. J., & Campbell, K. H. (1997). Viable offspring derived from fetal and adult mammalian cells. Nature, 385, 810–813.PubMedCrossRefGoogle Scholar
  105. 105.
    Wakayama, T., Perry, A. C., Zuccotti, M., Johnson, K. R., & Yanagimachi, R. (1998). Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature, 394, 369–374.PubMedCrossRefGoogle Scholar
  106. 106.
    Cibelli, J. B., Stice, S. L., Golueke, P. J., Kane, J. J., Jerry, J., Blackwell, C., et al. (1998). Cloned transgenic calves produced from nonquiescent fetal fibroblasts. Science, 280, 1256–1258.PubMedCrossRefGoogle Scholar
  107. 107.
    Betthauser, J., Forsberg, E., Augenstein, M., Childs, L., Eilertsen, K., Enos, J., et al. (2000). Production of cloned pigs from in vitro systems. Nature Biotechnology, 18, 1055–1059.PubMedCrossRefGoogle Scholar
  108. 108.
    Reggio, B. C., James, A. N., Green, H. L., Gavin, W. G., Behboodi, E., Echelard, Y., & Godke, R. A. (2001). Cloned transgenic offspring resulting from somatic cell nuclear transfer in the goat: oocytes derived from both follicle-stimulating hormone-stimulated and nonstimulated abattoir-derived ovaries. Biology of Reproduction, 65, 1528–1533.PubMedCrossRefGoogle Scholar
  109. 109.
    Chesné, P., Adenot, P. G., Viglietta, C., Baratte, M., Boulanger, L., & Renard, J. P. (2002). Cloned rabbits produced by nuclear transfer from adult somatic cells. Nature Biotechnology, 20, 366–369.PubMedCrossRefGoogle Scholar
  110. 110.
    Shin, T., Kraemer, D., Pryor, J., Liu, L., Rugila, J., & Howe, L. (2002). A cat cloned by nuclear transplantation. Nature, 415, 859.PubMedCrossRefGoogle Scholar
  111. 111.
    Rideout, W. Mr., Hochedlinger, K., Kyba, M., Daley, G. Q., & Jaenisch, R. (2002). Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy. Cell, 109, 17–27.PubMedCrossRefGoogle Scholar
  112. 112.
    Wakayama, T., Tabar, V., Rodriguez, I., Perry, A. C., Studer, L., & Mombaerts, P. (2001). Differentiation of embryonic stem cell lines generated from adult somatic cells by nuclear transfer. Science, 292, 740–743.PubMedCrossRefGoogle Scholar
  113. 113.
    Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126, 663–676.PubMedCrossRefGoogle Scholar
  114. 114.
    Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., et al. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131, 861–872.PubMedCrossRefGoogle Scholar
  115. 115.
    Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., et al. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science, 318(5858), 1917–1920.PubMedCrossRefGoogle Scholar
  116. 116.
    Blelloch, R., Venere, M., Yen, J., & Ramalho-Santos, M. (2007). Generation of induced pluripotent stem cells in the absence of drug selection. Cell Stem Cell, 1, 254–247.CrossRefGoogle Scholar
  117. 117.
    Wernig, M., Meissner, A., Foreman, R., Brambrink, T., Ku, M., Hochedlinger, K., et al. (2007). In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature, 448, 318–324.PubMedCrossRefGoogle Scholar
  118. 118.
    Park, I. H., Zhao, R., West, J. A., Yabuuchi, A., Huo, H., Ince, T. A., et al. (2008). Reprogramming of human somatic cells to pluripotency with defined factors. Nature, 451, 141–146.PubMedCrossRefGoogle Scholar
  119. 119.
    Byrne, J. A., Pedersen, D. A., Clepper, L. L., Nelson, M., Sanger, W. G., Gokhale, S., et al. (2007). Producing primate embryonic stem cells by somatic cell nuclear transfer. Nature, 450, 497–502.PubMedCrossRefGoogle Scholar
  120. 120.
    Hanna, J. W. M., Markoulaki, S., Sun, C. W., Meissner, A., Cassady, J. P., Beard, C., et al. (2007). Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science, 318, 1920–1923.PubMedCrossRefGoogle Scholar
  121. 121.
    Wernig, M., Zhao, J. P., Pruszak, J., Hedlund, E., Fu, D., Soldner, F., et al. (2008). Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proceedings of the National Academy of Sciences of the United States of America, 105, 5856–5861.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press 2008

Authors and Affiliations

  • Radbod Darabi
    • 1
  • Filipe N. C. Santos
    • 1
  • Rita C. R. Perlingeiro
    • 1
    • 2
  1. 1.Department of Developmental BiologyUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Lillehei Heart Institute, Department of MedicineUniversity of MinnesotaMinneapolisUSA

Personalised recommendations