Stem Cell Reviews and Reports

, Volume 6, Issue 3, pp 367–380

Advances in Reprogramming Somatic Cells to Induced Pluripotent Stem Cells



Traditionally, nuclear reprogramming of cells has been performed by transferring somatic cell nuclei into oocytes, by combining somatic and pluripotent cells together through cell fusion and through genetic integration of factors through somatic cell chromatin. All of these techniques changes gene expression which further leads to a change in cell fate. Here we discuss recent advances in generating induced pluripotent stem cells, different reprogramming methods and clinical applications of iPS cells. Viral vectors have been used to transfer transcription factors (Oct4, Sox2, c-myc, Klf4, and nanog) to induce reprogramming of mouse fibroblasts, neural stem cells, neural progenitor cells, keratinocytes, B lymphocytes and meningeal membrane cells towards pluripotency. Human fibroblasts, neural cells, blood and keratinocytes have also been reprogrammed towards pluripotency. In this review we have discussed the use of viral vectors for reprogramming both animal and human stem cells. Currently, many studies are also involved in finding alternatives to using viral vectors carrying transcription factors for reprogramming cells. These include using plasmid transfection, piggyback transposon system and piggyback transposon system combined with a non viral vector system. Applications of these techniques have been discussed in detail including its advantages and disadvantages. Finally, current clinical applications of induced pluripotent stem cells and its limitations have also been reviewed. Thus, this review is a summary of current research advances in reprogramming cells into induced pluripotent stem cells.


Induced pluripotent stem cells Embryonic stem cells Adult stem cell Viral vectors Transcription factor Regenerative medicine Reprogram Somatic cells 


  1. 1.
    Aasen, T., Raya, A., Barrero, M. J., Garreta, E., Consiglio, A., Gonzalez, F., et al. (2008). Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nature Biotechnology, 26(11), 1276–1284.PubMedCrossRefGoogle Scholar
  2. 2.
    Agarwal, S. (2006). Cellular reprogramming. Methods in Enzymology, 420, 265–283.PubMedCrossRefGoogle Scholar
  3. 3.
    Amabile, G., & Meissner, A. (2009). Induced pluripotent stem cells: current progress and potential for regenerative medicine. Trends in Molecular Medicine, 15(2), 59–68.PubMedCrossRefGoogle Scholar
  4. 4.
    Andrews, P. W., & Goodfellow, P. N. (1980). Antigen expression by somatic cell hybrids of a murine embryonal carcinoma cell with thymocytes and L cells. Somatic Cell Genetics, 6(2), 271–284.PubMedCrossRefGoogle Scholar
  5. 5.
    Avilion, A. A., Nicolis, S. K., Pevny, L. H., Perez, L., Vivian, N., & Lovell-Badge, R. (2003). Multipotent cell lineages in early mouse development depend on SOX2 function. Genes and Development, 17(1), 126–140.PubMedCrossRefGoogle Scholar
  6. 6.
    Barroca, V., Lassalle, B., Coureuil, M., Louis, J. P., Le Page, F., Testart, J., et al. (2009). Mouse differentiating spermatogonia can generate germinal stem cells in vivo. Nature Cell Biology, 11(2), 190–196.PubMedCrossRefGoogle Scholar
  7. 7.
    Ben-Shushan, E., Thompson, J. R., Gudas, L. J., & Bergman, Y. (1998). Rex-1, a gene encoding a transcription factor expressed in the early embryo, is regulated via Oct-3/4 and Oct-6 binding to an octamer site and a novel protein, Rox-1, binding to an adjacent site. Molecular and Cellular Biology, 18(4), 1866–1878.PubMedGoogle Scholar
  8. 8.
    Beyhan, Z., Iager, A. E., & Cibelli, J. B. (2007). Interspecies nuclear transfer: implications for embryonic stem cell biology. Cell Stem Cell, 1(5), 502–512.PubMedCrossRefGoogle Scholar
  9. 9.
    Boiani, M., Eckardt, S., Scholer, H. R., & McLaughlin, K. J. (2002). Oct4 distribution and level in mouse clones: consequences for pluripotency. Genes and Development, 16(10), 1209–1219.PubMedCrossRefGoogle Scholar
  10. 10.
    Brem, G., & Kuhholzer, B. (2002). The recent history of somatic cloning in mammals. Cloning Stem Cells, 4(1), 57–63.PubMedCrossRefGoogle Scholar
  11. 11.
    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(7169), 497–502.PubMedCrossRefGoogle Scholar
  12. 12.
    Campbell, K. H., Fisher, P., Chen, W. C., Choi, I., Kelly, R. D., Lee, J. H., et al. (2007). Somatic cell nuclear transfer: past, present and future perspectives. Theriogenology, 68(Suppl 1), S214–S231.PubMedCrossRefGoogle Scholar
  13. 13.
    Chambers, S. M., Fasano, C. A., Papapetrou, E. P., Tomishima, M., Sadelain, M., & Studer, L. (2009). Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nature Biotechnology, 27(3), 275–280.PubMedCrossRefGoogle Scholar
  14. 14.
    Cheng, L., Sung, M. T., Cossu-Rocca, P., Jones, T. D., MacLennan, G. T., De Jong, J., et al. (2007). OCT4: biological functions and clinical applications as a marker of germ cell neoplasia. Journal of Pathology, 211(1), 1–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Cowan, C. A., Atienza, J., Melton, D. A., & Eggan, K. (2005). Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science, 309(5739), 1369–1373.PubMedCrossRefGoogle Scholar
  16. 16.
    Dimos, J. T., Rodolfa, K. T., Niakan, K. K., Weisenthal, L. M., Mitsumoto, H., Chung, W., et al. (2008). Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science, 321(5893), 1218–1221.PubMedCrossRefGoogle Scholar
  17. 17.
    Do, J. T., & Scholer, H. R. (2004). Nuclei of embryonic stem cells reprogram somatic cells. Stem Cells, 22(6), 941–949.PubMedCrossRefGoogle Scholar
  18. 18.
    Do, J. T., & Scholer, H. R. (2006). Cell-cell fusion as a means to establish pluripotency. Ernst Schering Research Foundation Workshop, 60(60), 35–45.Google Scholar
  19. 19.
    Duinsbergen, D., Eriksson, M., t Hoen, P. A., Frisen, J., & Mikkers, H. (2008). Induced pluripotency with endogenous and inducible genes. Experimental Cell Research, 314(17), 3255–3263.PubMedCrossRefGoogle Scholar
  20. 20.
    Ebert, A. D., Yu, J., Rose, F. F., Jr., Mattis, V. B., Lorson, C. L., Thomson, J. A., et al. (2009). Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature, 457(7227), 277–280.PubMedCrossRefGoogle Scholar
  21. 21.
    Egli, D., Rosains, J., Birkhoff, G., & Eggan, K. (2007). Developmental reprogramming after chromosome transfer into mitotic mouse zygotes. Nature, 447(7145), 679–685.PubMedCrossRefGoogle Scholar
  22. 22.
    Ellis, P., Fagan, B. M., Magness, S. T., Hutton, S., Taranova, O., Hayashi, S., et al. (2004). SOX2, a persistent marker for multipotential neural stem cells derived from embryonic stem cells, the embryo or the adult. Developmental Neuroscience, 26(2–4), 148–165.PubMedCrossRefGoogle Scholar
  23. 23.
    Eminli, S., Utikal, J., Arnold, K., Jaenisch, R., & Hochedlinger, K. (2008). Reprogramming of neural progenitor cells into induced pluripotent stem cells in the absence of exogenous Sox2 expression. Stem Cells, 26(10), 2467–2474.PubMedCrossRefGoogle Scholar
  24. 24.
    Feng, B., Jiang, J., Kraus, P., Ng, J. H., Heng, J. C., Chan, Y. S., et al. (2009). Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb. Nature Cell Biology, 11(2), 197–203.PubMedCrossRefGoogle Scholar
  25. 25.
    Flake, A. W., & Zanjani, E. D. (1997). Cellular therapy. Obstetrics and Gynecology Clinics of North America, 24(1), 159–177.PubMedCrossRefGoogle Scholar
  26. 26.
    Flasza, M., Shering, A. F., Smith, K., Andrews, P. W., Talley, P., & Johnson, P. A. (2003). Reprogramming in inter-species embryonal carcinoma-somatic cell hybrids induces expression of pluripotency and differentiation markers. Cloning Stem Cells, 5(4), 339–354.PubMedCrossRefGoogle Scholar
  27. 27.
    Foster, K. W., Liu, Z., Nail, C. D., Li, X., Fitzgerald, T. J., Bailey, S. K., et al. (2005). Induction of KLF4 in basal keratinocytes blocks the proliferation-differentiation switch and initiates squamous epithelial dysplasia. Oncogene, 24(9), 1491–1500.PubMedCrossRefGoogle Scholar
  28. 28.
    Fulka, J., Jr., First, N. L., Loi, P., & Moor, R. M. (1998). Cloning by somatic cell nuclear transfer. Bioessays, 20(10), 847–851.PubMedCrossRefGoogle Scholar
  29. 29.
    Fulka, J., Jr., Loi, P., Fulka, H., Ptak, G., & Nagai, T. (2004). Nucleus transfer in mammals: noninvasive approaches for the preparation of cytoplasts. Trends in Biotechnology, 22(6), 279–283.PubMedCrossRefGoogle Scholar
  30. 30.
    Gaudet, F., Hodgson, J. G., Eden, A., Jackson-Grusby, L., Dausman, J., Gray, J. W., et al. (2003). Induction of tumors in mice by genomic hypomethylation. Science, 300(5618), 489–492.PubMedCrossRefGoogle Scholar
  31. 31.
    Gearhart, J., Pashos, E. E., & Prasad, M. K. (2007). Pluripotency redux–advances in stem-cell research. New England Journal of Medicine, 357(15), 1469–1472.PubMedCrossRefGoogle Scholar
  32. 32.
    Gmur, R., Solter, D., & Knowles, B. B. (1980). Independent regulation of H-2K and H-2D gene expression in murine teratocarcinoma somatic cell hybrids. Journal of Experimental Medicine, 151(6), 1349–1359.PubMedCrossRefGoogle Scholar
  33. 33.
    Gonzales, C., & Pedrazzini, T. (2009). Progenitor cell therapy for heart disease. Experimental Cell Research, 315(18), 3077–3085.Google Scholar
  34. 34.
    Grinnell, K. L., Yang, B., Eckert, R. L., & Bickenbach, J. R. (2007). De-differentiation of mouse interfollicular keratinocytes by the embryonic transcription factor Oct-4. Journal of Investigative Dermatology, 127(2), 372–380.PubMedCrossRefGoogle Scholar
  35. 35.
    Gurdon, J. B., & Melton, D. A. (2008). Nuclear reprogramming in cells. Science, 322(5909), 1811–1815.PubMedCrossRefGoogle Scholar
  36. 36.
    Hanna, J., Wernig, M., Markoulaki, S., Sun, C. W., Meissner, A., Cassady, J. P., et al. (2007). Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science, 318(5858), 1920–1923.PubMedCrossRefGoogle Scholar
  37. 37.
    Hanna, J., Markoulaki, S., Schorderet, P., Carey, B. W., Beard, C., Wernig, M., et al. (2008). Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell, 133(2), 250–264.PubMedCrossRefGoogle Scholar
  38. 38.
    Hanna, J., Saha, K., Pando, B., Zon, J., Lenger, C., & Creyghton, M. (2009). Direct cell reprogramming is a stochastic process amenable to acceleration. Nature, 462, 595–601.PubMedCrossRefGoogle Scholar
  39. 39.
    Heyman, Y., Vignon, X., Chesne, P., Le Bourhis, D., Marchal, J., & Renard, J. P. (1998). Cloning in cattle: from embryo splitting to somatic nuclear transfer. Reproduction, Nutrition, Development, 38(6), 595–603.PubMedCrossRefGoogle Scholar
  40. 40.
    Hiiragi, T., & Solter, D. (2005). Reprogramming is essential in nuclear transfer. Molecular Reproduction and Development, 70(4), 417–421.PubMedCrossRefGoogle Scholar
  41. 41.
    Hochedlinger, K., & Jaenisch, R. (2002). Nuclear transplantation: lessons from frogs and mice. Current Opinion in Cell Biology, 14(6), 741–748.PubMedCrossRefGoogle Scholar
  42. 42.
    Hochedlinger, K., & Jaenisch, R. (2003). Nuclear transplantation, embryonic stem cells, and the potential for cell therapy. New England Journal of Medicine, 349(3), 275–286.PubMedCrossRefGoogle Scholar
  43. 43.
    Hochedlinger, K., & Jaenisch, R. (2006). Nuclear reprogramming and pluripotency. Nature, 441(7097), 1061–1067.PubMedCrossRefGoogle Scholar
  44. 44.
    Hochedlinger, K., & Plath, K. (2009). Epigenetic reprogramming and induced pluripotency. Development, 136(4), 509–523.PubMedCrossRefGoogle Scholar
  45. 45.
    Hochedlinger, K., Rideout, W. M., Kyba, M., Daley, G. Q., Blelloch, R., & Jaenisch, R. (2004). Nuclear transplantation, embryonic stem cells and the potential for cell therapy. Hematology Journal, 5(Suppl 3), S114–S117.PubMedCrossRefGoogle Scholar
  46. 46.
    Hochedlinger, K., Yamada, Y., Beard, C., & Jaenisch, R. (2005). Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell, 121(3), 465–477.PubMedCrossRefGoogle Scholar
  47. 47.
    Hotta, A., & Ellis, J. (2008). Retroviral vector silencing during iPS cell induction: an epigenetic beacon that signals distinct pluripotent states. Journal of Cellular Biochemistry, 105(4), 940–948.PubMedCrossRefGoogle Scholar
  48. 48.
    Huangfu, D., Maehr, R., Guo, W., Eijkelenboom, A., Snitow, M., Chen, A. E., et al. (2008). Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nature Biotechnology, 26(7), 795–797.PubMedCrossRefGoogle Scholar
  49. 49.
    Huangfu, D., Osafune, K., Maehr, R., Guo, W., Eijkelenboom, A., Chen, S., et al. (2008). Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nature Biotechnology, 26(11), 1269–1275.PubMedCrossRefGoogle Scholar
  50. 50.
    Ichida, J., Blanchard, J., Lam, K., Son, E., Chung, J., Egli, D., et al. (2009). A small molecule inhibitor of TGF-beta signaling replaces Sox2 in reprogramming by inducing Nanog. Cell Stem Cell, 5, 491–503.PubMedCrossRefGoogle Scholar
  51. 51.
    Jaenisch, R., Hochedlinger, K., Blelloch, R., Yamada, Y., Baldwin, K., & Eggan, K. (2004). Nuclear cloning, epigenetic reprogramming, and cellular differentiation. Cold Spring Harbor Symposia on Quantitative Biology, 69, 19–27.PubMedGoogle Scholar
  52. 52.
    Kaji, K., Norrby, K., Paca, A., Mileikovsky, M., Mohseni, P., & Woltjen, K. (2009). Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature, 458(7239), 771–775.PubMedCrossRefGoogle Scholar
  53. 53.
    Kaji, K., Norrby, K., Paca, A., Mileikovsky, M., Mohseni, P., & Woltjen, K. (2009). Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature, 458(7239), 771–775.Google Scholar
  54. 54.
    Kim, J. B., Zaehres, H., Wu, G., Gentile, L., Ko, K., Sebastiano, V., et al. (2008). Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature, 454(7204), 646–650.PubMedCrossRefGoogle Scholar
  55. 55.
    Kim, J. B., Sebastiano, V., Wu, G., Arauzo-Bravo, M. J., Sasse, P., Gentile, L., et al. (2009). Oct4-induced pluripotency in adult neural stem cells. Cell, 136(3), 411–419.PubMedCrossRefGoogle Scholar
  56. 56.
    Kimura, H., Tada, M., Nakatsuji, N., & Tada, T. (2004). Histone code modifications on pluripotential nuclei of reprogrammed somatic cells. Molecular and Cellular Biology, 24(13), 5710–5720.PubMedCrossRefGoogle Scholar
  57. 57.
    Korsgren, O., & Nilsson, B. (2009). Improving islet transplantation: a road map for a widespread application for the cure of persons with type I diabetes. Current Opinion in Organ Transplantion, 14(6), 683–687.Google Scholar
  58. 58.
    Kosaka, N., Kodama, M., Sasaki, H., Yamamoto, Y., Takeshita, F., Takahama, Y., et al. (2006). FGF-4 regulates neural progenitor cell proliferation and neuronal differentiation. FASEB Journal, 20(9), 1484–1485.PubMedCrossRefGoogle Scholar
  59. 59.
    Liu, S. V. (2008). iPS cells: a more critical review. Stem Cells Dev, 17(3), 391–397.PubMedCrossRefGoogle Scholar
  60. 60.
    Loh, Y. H., Wu, Q., Chew, J. L., Vega, V. B., Zhang, W., Chen, X., et al. (2006). The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nature Genetics, 38(4), 431–440.PubMedCrossRefGoogle Scholar
  61. 61.
    Loh, Y. H., Agarwal, S., Park, I. H., Urbach, A., Huo, H., Heffner, G. C., et al. (2009). Generation of induced pluripotent stem cells from human blood. Blood, 113(22), 5476–5479.Google Scholar
  62. 62.
    Lopez Moratalla, N. (2008). Ethical principles in research related to regenerative therapy. Cuadernos de BioeÂtica, 19(66), 195–210.Google Scholar
  63. 63.
    Maherali, N., & Hochedlinger, K. (2008). Guidelines and techniques for the generation of induced pluripotent stem cells. Cell Stem Cell, 3(6), 595–605.PubMedCrossRefGoogle Scholar
  64. 64.
    Maherali, N., Sridharan, R., Xie, W., Utikal, J., Eminli, S., Arnold, K., et al. (2007). Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell, 1(1), 55–70.PubMedCrossRefGoogle Scholar
  65. 65.
    Masui, S., Nakatake, Y., Toyooka, Y., Shimosato, D., Yagi, R., Takahashi, K., et al. (2007). Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nature Cell Biology, 9(6), 625–635.PubMedCrossRefGoogle Scholar
  66. 66.
    Miller, R. A., & Ruddle, F. H. (1976). Pluripotent teratocarcinoma-thymus somatic cell hybrids. Cell, 9(1), 45–55.PubMedCrossRefGoogle Scholar
  67. 67.
    Nakagawa, M., Koyanagi, M., Tanabe, K., Takahashi, K., Ichisaka, T., Aoi, T., et al. (2008). Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nature Biotechnology, 26(1), 101–106.PubMedCrossRefGoogle Scholar
  68. 68.
    Niwa, H., Miyazaki, J., & Smith, A. G. (2000). Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nature Genetics, 24(4), 372–376.PubMedCrossRefGoogle Scholar
  69. 69.
    Odorico, J. S., Kaufman, D. S., & Thomson, J. A. (2001). Multilineage differentiation from human embryonic stem cell lines. Stem Cells, 19(3), 193–204.PubMedCrossRefGoogle Scholar
  70. 70.
    Okita, K., Ichisaka, T., & Yamanaka, S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature, 448(7151), 313–317.PubMedCrossRefGoogle Scholar
  71. 71.
    Okita, K., Nakagawa, M., Hyenjong, H., Ichisaka, T., & Yamanaka, S. (2008). Generation of mouse induced pluripotent stem cells without viral vectors. Science, 322(5903), 949–953.PubMedCrossRefGoogle Scholar
  72. 72.
    Okuda, A., Fukushima, A., Nishimoto, M., Orimo, A., Yamagishi, T., Nabeshima, Y., et al. (1998). UTF1, a novel transcriptional coactivator expressed in pluripotent embryonic stem cells and extra-embryonic cells. EMBO Journal, 17(7), 2019–2032.PubMedCrossRefGoogle Scholar
  73. 73.
    Ovitt, C. E., & Scholer, H. R. (1998). The molecular biology of Oct-4 in the early mouse embryo. Molecular Human Reproduction, 4(11), 1021–1031.PubMedCrossRefGoogle Scholar
  74. 74.
    Pan, G., Li, J., Zhou, Y., Zheng, H., & Pei, D. (2006). A negative feedback loop of transcription factors that controls stem cell pluripotency and self-renewal. FASEB Journal, 20(10), 1730–1732.PubMedCrossRefGoogle Scholar
  75. 75.
    Park, I. H., Arora, N., Huo, H., Maherali, N., Ahfeldt, T., Shimamura, A., et al. (2008). Disease-specific induced pluripotent stem cells. Cell, 134(5), 877–886.PubMedCrossRefGoogle Scholar
  76. 76.
    Pera, M. F., Reubinoff, B., & Trounson, A. (2000). Human embryonic stem cells. Journal of Cell Science, 113(Pt 1), 5–10.PubMedGoogle Scholar
  77. 77.
    Qin, D., Gan, Y., Shao, K., Wang, H., Li, W., Wang, T., et al. (2008). Mouse meningiocytes express Sox2 and yield high efficiency of chimeras after nuclear reprogramming with exogenous factors. Journal of Biological Chemistry, 283(48), 33730–33735.PubMedCrossRefGoogle Scholar
  78. 78.
    Rao, M., & Condic, M. L. (2008). Alternative sources of pluripotent stem cells: scientific solutions to an ethical dilemma. Stem Cells Dev, 17(1), 1–10.PubMedCrossRefGoogle Scholar
  79. 79.
    Renard, J. P. (1998). Chromatin remodelling and nuclear reprogramming at the onset of embryonic development in mammals. Reproduction, Fertility, and Development, 10(7–8), 573–580.PubMedCrossRefGoogle Scholar
  80. 80.
    Rhind, S. M., Taylor, J. E., De Sousa, P. A., King, T. J., McGarry, M., & Wilmut, I. (2003). Human cloning: can it be made safe? Nature Reviews. Genetics, 4(11), 855–864.PubMedCrossRefGoogle Scholar
  81. 81.
    Rideout, W. M., 3rd, Eggan, K., & Jaenisch, R. (2001). Nuclear cloning and epigenetic reprogramming of the genome. Science, 293(5532), 1093–1098.PubMedCrossRefGoogle Scholar
  82. 82.
    Shevchenko, A. I., Medvedev, S. P., Mazurok, N. A., & Zakiian, S. M. (2009). Induced pluripotent stem cells. Genetika, 45(2), 160–168.PubMedGoogle Scholar
  83. 83.
    Soldner, F., Hockemeyer, D., Beard, C., Gao, Q., Bell, G. W., Cook, E. G., et al. (2009). Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell, 136(5), 964–977.PubMedCrossRefGoogle Scholar
  84. 84.
    Solter, D. (2000). Mammalian cloning: advances and limitations. Nature Reviews. Genetics, 1(3), 199–207.PubMedCrossRefGoogle Scholar
  85. 85.
    Stadtfeld, M., Nagaya, M., Utikal, J., Weir, G., & Hochedlinger, K. (2008). Induced pluripotent stem cells generated without viral integration. Science, 322(5903), 945–949.PubMedCrossRefGoogle Scholar
  86. 86.
    Strong, M., Farrugia, A., & Rebulla, P. (2009). Stem cell and cellular therapy developments. Biologicals, 37(2), 103–107.PubMedCrossRefGoogle Scholar
  87. 87.
    Sumi, T., Tsuneyoshi, N., Nakatsuji, N., & Suemori, H. (2007). Apoptosis and differentiation of human embryonic stem cells induced by sustained activation of c-Myc. Oncogene, 26(38), 5564–5576.PubMedCrossRefGoogle Scholar
  88. 88.
    Surani, M. A. (2005). Nuclear reprogramming by human embryonic stem cells. Cell, 122(5), 653–654.PubMedCrossRefGoogle Scholar
  89. 89.
    Tada, M., Tada, T., Lefebvre, L., Barton, S. C., & Surani, M. A. (1997). Embryonic germ cells induce epigenetic reprogramming of somatic nucleus in hybrid cells. EMBO Journal, 16(21), 6510–6520.PubMedCrossRefGoogle Scholar
  90. 90.
    Tada, M., Takahama, Y., Abe, K., Nakatsuji, N., & Tada, T. (2001). Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Current Biology, 11(19), 1553–1558.PubMedCrossRefGoogle Scholar
  91. 91.
    Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126(4), 663–676.PubMedCrossRefGoogle Scholar
  92. 92.
    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(5), 861–872.PubMedCrossRefGoogle Scholar
  93. 93.
    Taranger, C. K., Noer, A., Sorensen, A. L., Hakelien, A. M., Boquest, A. C., & Collas, P. (2005). Induction of dedifferentiation, genomewide transcriptional programming, and epigenetic reprogramming by extracts of carcinoma and embryonic stem cells. Molecular Biology of the Cell, 16(12), 5719–5735.PubMedCrossRefGoogle Scholar
  94. 94.
    Taura, D., Noguchi, M., Sone, M., Hosoda, K., Mori, E., Okada, Y., et al. (2009). Adipogenic differentiation of human induced pluripotent stem cells: comparison with that of human embryonic stem cells. FEBS Letters, 583(6), 1029–1033.PubMedCrossRefGoogle Scholar
  95. 95.
    Tsunoda, Y., & Kato, Y. (2000). Animal cloning by somatic nuclear transfer. Tanpakushitsu Kakusan Koso, 45(13 Suppl), 2015–2020.PubMedGoogle Scholar
  96. 96.
    Tweedell, K. S. (2008). New paths to pluripotent stem cells. Current Stem Cell Research & Therapy, 3(3), 151–162.CrossRefGoogle Scholar
  97. 97.
    Wade, P. A., & Kikyo, N. (2002). Chromatin remodeling in nuclear cloning. European Journal of Biochemistry, 269(9), 2284–2287.PubMedCrossRefGoogle Scholar
  98. 98.
    Wakayama, T., Shinkai, Y., Tamashiro, K. L., Niida, H., Blanchard, D. C., Blanchard, R. J., et al. (2000). Cloning of mice to six generations. Nature, 407(6802), 318–319.PubMedCrossRefGoogle Scholar
  99. 99.
    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(7151), 318–324.PubMedCrossRefGoogle Scholar
  100. 100.
    Wernig, M., Lengner, C. J., Hanna, J., Lodato, M. A., Steine, E., Foreman, R., et al. (2008). A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types. Nature Biotechnology, 26(8), 916–924.PubMedCrossRefGoogle Scholar
  101. 101.
    Wernig, M., Meissner, A., Cassady, J. P., & Jaenisch, R. (2008). c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell, 2(1), 10–12.PubMedCrossRefGoogle Scholar
  102. 102.
    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(6619), 810–813.PubMedCrossRefGoogle Scholar
  103. 103.
    Wilmut, I., Young, L., & Campbell, K. H. (1998). Embryonic and somatic cell cloning. Reproduction, Fertility, and Development, 10(7–8), 639–643.PubMedCrossRefGoogle Scholar
  104. 104.
    Woltjen, K., Michael, I. P., Mohseni, P., Desai, R., Mileikovsky, M., Hamalainen, R., et al. (2009). piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature, 458(7239), 766–770.Google Scholar
  105. 105.
    Yamanaka, S. (2008). Pluripotency and nuclear reprogramming. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 363(1500), 2079–2087.PubMedCrossRefGoogle Scholar
  106. 106.
    Yan, X., Qin, H., Qu, C., Tuan, R. S., Shi, S., & Huang, G. T. (2009). iPS cells reprogrammed from mesenchymal-like stem/progenitor cells of dental tissue origin. Stem Cells Dev, Oct 1 [Epub ahead of print].Google Scholar
  107. 107.
    Yang, X., Smith, S. L., Tian, X. C., Lewin, H. A., Renard, J. P., & Wakayama, T. (2007). Nuclear reprogramming of cloned embryos and its implications for therapeutic cloning. Nature Genetics, 39(3), 295–302.PubMedCrossRefGoogle Scholar
  108. 108.
    Ying, Q. L., Nichols, J., Evans, E. P., & Smith, A. G. (2002). Changing potency by spontaneous fusion. Nature, 416(6880), 545–548.PubMedCrossRefGoogle Scholar
  109. 109.
    Yu, J., Vodyanik, M. A., He, P., Slukvin, I. I., & Thomson, J. A. (2006). Human embryonic stem cells reprogram myeloid precursors following cell-cell fusion. Stem Cells, 24(1), 168–176.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Oral Biology, School of Dental MedicineThe State University of New York at BuffaloBuffaloUSA

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