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Progenitor Cells for Regenerative Medicine and Consequences of ART and Cloning-Associated Epimutations

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Abstract

The “holy grail” of regenerative medicine is the identification of an undifferentiated progenitor cell that is pluripotent, patient specific, and ethically unambiguous. Such a progenitor cell must also be able to differentiate into functional, transplantable tissue, while avoiding the risks of immune rejection. With reports detailing aberrant genomic imprinting associated with assisted reproductive technologies (ART) and reproductive cloning, the idea that human embryonic stem cells (hESCs) derived from surplus in vitro fertilized embryos or nuclear transfer ESCs (ntESCs) harvested from cloned embryos may harbor dangerous epigenetic errors has gained attention. Various progenitor cell sources have been proposed for human therapy, from hESCs to ntESCs, and from adult stem cells to induced pluripotent stem cells (iPS and piPS cells). This review highlights the advantages and disadvantages of each of these technologies, with particular emphasis on epigenetic stability.

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References

  1. Metallo, C., Azarin, S., Ji, L., de Pablo, J., & Palecek, S. (2008). Engineering tissue from human embryonic stem cells. Journal of Cellular and Molecular Medicine, 12(3), 709–729.

    Article  CAS  Google Scholar 

  2. Pierce, G., & Speers, W. (1988). Tumors as caricatures of the process of tissue renewal: Prospects for therapy by directing differentiation. Cancer Research, 48(8), 1996–2004.

    CAS  Google Scholar 

  3. Tögel, F., & Westenfelder, C. (2007). Adult bone marrow-derived stem cells for organ regeneration and repair. Developmental Dynamics, 236(12), 3321–3331.

    Article  CAS  Google Scholar 

  4. Zuk, P., Zhu, M., Mizuno, H., Huang, J., Futrell, J., Katz, A., et al. (2001). Multilineage cells from human adipose tissue: Implications for cell-based therapies. Tissue Engineering, 7(2), 211–228.

    Article  CAS  Google Scholar 

  5. Roisen, F., Klueber, K., Lu, C., Hatcher, L., Dozier, A., Shields, C., et al. (2001). Adult human olfactory stem cells. Brain Research, 890(1), 11–22.

    Article  CAS  Google Scholar 

  6. Clarke, D., Johansson, C., Wilbertz, J., Veress, B., Nilsson, E., Karlström, H., et al. (2000). Generalized potential of adult neural stem cells. Science, 288(5471), 1660–1663.

    Article  CAS  Google Scholar 

  7. Geiger, H., Sick, S., Bonifer, C., & Müller, A. (1998). Globin gene expression is reprogrammed in chimeras generated by injecting adult hematopoietic stem cells into mouse blastocysts. Cell, 93(6), 1055–1065.

    Article  CAS  Google Scholar 

  8. Raff, M. (2003). Adult stem cell plasticity: Fact or artifact? Annual Review of Cell and Developmental Biology, 19, 1–22.

    Article  CAS  Google Scholar 

  9. Marcus, A., & Woodbury, D. (2008). Fetal stem cells from extra-embryonic tissues: Do not discard. Journal of Cellular and Molecular Medicine, 12(3), 730–742.

    Article  CAS  Google Scholar 

  10. Smith, A. (2001). Embryo-derived stem cells: Of mice and men. Annual Review of Cell and Developmental Biology, 17, 435–462.

    Google Scholar 

  11. Thomson, J., Itskovitz-Eldor, J., Shapiro, S., Waknitz, M., Swiergiel, J., Marshall, V., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282(5391), 1145–1147.

    Article  CAS  Google Scholar 

  12. Ludwig, T., Levenstein, M., Jones, J., Berggren, W., Mitchen, E., Frane, J., et al. (2006). Derivation of human embryonic stem cells in defined conditions. Nature Biotechnology, 24(2), 185–187.

    Article  CAS  Google Scholar 

  13. Hentze, H., Graichen, R., & Colman, A. (2007). Cell therapy and the safety of embryonic stem cell-derived grafts. Trends in Biotechnology, 25(1), 24–32.

    Article  CAS  Google Scholar 

  14. Baylis, F., & McLeod, C. (2007). The stem cell debate continues: The buying and selling of eggs for research. Journal of Medical Ethics, 33(12), 726–731.

    Article  CAS  Google Scholar 

  15. Lawrence, L. T., & Moley, K. H. (2008). Epigenetics and assisted reproductive technologies: Human imprinting syndromes. Seminars in Reproductive Medicine, 26(2), 143–152.

    Article  CAS  Google Scholar 

  16. Meissner, A., & Jaenisch, R. (2006). Mammalian nuclear transfer. Developmental Dynamics, 235, 2460–2469.

    Article  Google Scholar 

  17. Allegrucci, C., Denning, C., Priddle, H., & Young, L. (2004). Stem-cell consequences of embryo epigenetic defects. Lancet, 364, 206–208.

    Article  Google Scholar 

  18. Huntriss, J., & Picton, H. (2008). Stability of genomic imprinting in embryonic stem cells: Lessons from assisted reproductive technology. Current Stem Cell Research &Therapy, 3(2), 107–116.

    Article  CAS  Google Scholar 

  19. Drukker, M., Katz, G., Urbach, A., Schuldiner, M., Markel, G., Itskovitz-Eldor, J., et al. (2002). Characterization of the expression of MHC proteins in human embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 99(15), 9864–9869.

    Article  CAS  Google Scholar 

  20. Taylor, C., Bolton, E., Pocock, S., Sharples, L., Pedersen, R., & Bradley, J. (2005). Banking on human embryonic stem cells: Estimating the number of donor cell lines needed for HLA matching. Lancet, 366, 2019–2025.

    Article  Google Scholar 

  21. Vallier, L., Rugg-Gunn, P., Bouhon, I., Andersson, F., Sadler, A., & Pedersen, R. (2004). Enhancing and diminishing gene function in human embryonic stem cells. Stem Cells, 22(1), 2–11.

    Article  CAS  Google Scholar 

  22. Watanabe, K., Ueno, M., Kamiya, D., Nishiyama, A., Matsumura, M., Wataya, T., et al. (2007). A ROCK inhibitor permits survival of dissociated human embryonic stem cells. Nature Biotechnology, 25(6), 681–686.

    Article  CAS  Google Scholar 

  23. Zaehres, H., Lensch, M., Daheron, L., Stewart, S., Itskovitz-Eldor, J., & Daley, G. (2005). High-efficiency RNA interference in human embryonic stem cells. Stem Cells, 23(3), 299–305.

    Article  CAS  Google Scholar 

  24. Zwaka, T., & Thomson, J. (2003). Homologous recombination in human embryonic stem cells. Nature Biotechnology, 21(3), 319–321.

    Article  CAS  Google Scholar 

  25. McKinney-Freeman, S., & Daley, G. (2007). Derivation of hematopoietic stem cells from murine embryonic stem cells. Journal of Visualized Experiments, 25(2), 162.

    Google Scholar 

  26. Nair, V. (2008). Retrovirus-induced oncogenesis and safety of retroviral vectors. Current Opinion in Molecular Therapeutics, 10(5), 431–438.

    CAS  Google Scholar 

  27. Lanza, R., Chung, H., Yoo, J., Wettstein, P., Blackwell, C., Borson, N., et al. (2002). Generation of histocompatible tissues using nuclear transplantation. Nature Biotechnology, 20(7), 689–696.

    Article  CAS  Google Scholar 

  28. Wakayama, T., Tabar, V., Rodriguez, I., Perry, A., Studer, L., & Mombaerts, P. (2001). Differentiation of embryonic stem cell lines generated from adult somatic cells by nuclear transfer. Science, 292(5517), 740–743.

    Article  CAS  Google Scholar 

  29. Rideout, W., Hochedlinger, K., Kyba, M., Daley, G., & Jaenisch, R. (2002). Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy. Cell, 109, 17–27.

    Article  CAS  Google Scholar 

  30. Jiang, W., Bai, Z., Zhang, D., Shi, Y., Yong, J., Chen, S., et al. (2008). Differentiation of mouse nuclear transfer embryonic stem cells into functional pancreatic beta cells. Diabetologia, 51(9), 1671–1679.

    Article  CAS  Google Scholar 

  31. Byrne, J., Pedersen, D., Clepper, L., Nelson, M., Sanger, W., Gokhale, S., et al. (2007). Producing primate embryonic stem cells by somatic cell nuclear transfer. Nature, 450(7169), 497–502.

    Article  CAS  Google Scholar 

  32. Greda, P., Karasiewicz, J., & Modlinski, J. (2006). Mouse zygotes as recipients in embryo cloning. Reproduction, 132(5), 741–748.

    Article  CAS  Google Scholar 

  33. Ambrosi, D., Tanasijevic, B., Kaur, A., Obergfell, C., O’Neill, R., Krueger, W., et al. (2007). Genome-wide reprogramming in hybrids of somatic cells and embryonic stem cells. Stem Cells, 25(5), 1104–1113.

    Article  CAS  Google Scholar 

  34. Cowan, C., Atienza, J., Melton, D., & Eggan, K. (2005). Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science, 309(5739), 1369–1373.

    Article  CAS  Google Scholar 

  35. Matsumura, H., Tada, M., Otsuji, T., Yasuchika, K., Nakatsuji, N., Surani, A., et al. (2007). Targeted chromosome elimination from ES-somatic hybrid cells. Nature Methods, 4(1), 23–25.

    Article  CAS  Google Scholar 

  36. Vogelstein, B., Alberts, B., & Shine, K. (2002). Please don’t call it cloning! Science, 295, 1237.

  37. Klimanskaya, I., Chung, Y., Becker, S., Lu, S., & Lanza, R. (2006). Human embryonic stem cell lines derived from single blastomeres. Nature, 444(7118), 481–485.

    Article  CAS  Google Scholar 

  38. Goossens, V., De Rycke, M., De Vos, A., Staessen, C., Michiels, A., Verpoest, W., et al. (2008). Diagnostic efficiency, embryonic development and clinical outcome after the biopsy of one or two blastomeres for preimplantation genetic diagnosis. Human Reproduction, 23(3), 481–492.

    Article  Google Scholar 

  39. Baruffi, R., Mauri, A., Petersen, C., Nicoletti, A., Pontes, A., Oliveira, J., et al. (2009). Single-embryo transfer reduces clinical pregnancy rates and live births in fresh IVF and Intracytoplasmic Sperm Injection (ICSI) cycles: A meta-analysis. Reproductive Biology and Endocrinology, 7, 36.

    Google Scholar 

  40. Meissner, A., & Jaenisch, R. (2006). Generation of nuclear transfer-derived pluripotent ES cells from cloned Cdx2-deficient blastocysts. Nature, 439(7073), 212–215.

    Article  CAS  Google Scholar 

  41. Hurlbut, W. (2007). Ethics and embryonic stem cell research: Altered nuclear transfer as a way forward. BioDrugs, 21(2), 79–83.

    Article  CAS  Google Scholar 

  42. Kaufman, M., Robertson, E., Handyside, A., & Evans, M. (1983). Establishment of pluripotential cell lines from haploid mouse embryos. Journal of Embryology & Experimental Morphology, 73, 249–261.

    CAS  Google Scholar 

  43. Cibelli, J., Grant, K., Chapman, K., Cunniff, K., Worst, T., Green, H., et al. (2002). Parthenogenetic stem cells in nonhuman primates. Science, 295(5556), 819.

    Article  CAS  Google Scholar 

  44. Dighe, V., Clepper, L. P. D., Byrne, J., Ferguson, B., Gokhale, S., Penedo, M., et al. (2008). Heterozygous embryonic stem cell lines derived from nonhuman primate parthenotes. Stem Cells, 26, 756–766.

    Article  CAS  Google Scholar 

  45. Vrana, K., Hipp, J., Goss, A., McCool, B., Riddle, D., Walker, S., et al. (2003). Nonhuman primate parthenogenetic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 100(Suppl. 1), 11911–11916.

    Article  CAS  Google Scholar 

  46. Kim, K., Ng, K., Rugg-Gunn, P., Shieh, J., Kirak, O., Jaenisch, R., et al. (2007). Recombination signatures distinguish embryonic stem cells derived by parthenogenesis and somatic cell nuclear transfer. Cell Stem Cell, 1(3), 346–352.

    Article  CAS  Google Scholar 

  47. Mai, Q., Yu, Y., Li, T., Wang, L., Chen, M.-J., Huang, S.-Z., et al. (2007). Derivation of human embryonic stem cell lines from parthenogenetic blastocysts. Cell Research, 17, 1008–1019.

    Article  CAS  Google Scholar 

  48. Revazova, E., Turovets, N., Kochetkova, O., Kindarova, L., Kuzmichev, L., Janus, J., et al. (2007). Patient-specific stem cell lines derived from human parthenogenetic blastocysts. Cloning and Stem Cells, 9(3), 432–439.

    Article  CAS  Google Scholar 

  49. Kim, K., Lerou, P., Yabuuchi, A., Lengerke, C., Ng, K., West, J., et al. (2007). Histocompatible embryonic stem cells by parthenogenesis. Science, 315(5811), 482–486.

    Article  CAS  Google Scholar 

  50. Revazova, E., Turovets, N., Kochetkova, O., Aqapova, L., Sebastian, J., Pryzhkova, M., et al. (2008). HLA homozygous stem cell lines derived from human parthenogenetic blastocysts. Cloning and Stem Cells, 10(1), 11–24.

    Article  CAS  Google Scholar 

  51. Lampton, P., Crooker, R., Newmark, J., & Warner, C. (2008). Expression of MHC class I proteins and their antigen processing chaperones in mouse embryonic stem cells from fertilized and parthenogenetic embryos. Tissue Antigens, 72(5), 448–457.

    Article  CAS  Google Scholar 

  52. Teramura, T., Onodera, Y., Murakami, H., Ito, S., Mihara, T., Takehara, T., et al. (2009). Mouse androgenetic embryonic stem cells differentiated to multiple cell lineages in three embryonic germ layers in vitro. Journal of Reproduction and Development, 55(3), 283–292.

    Article  CAS  Google Scholar 

  53. Eckardt, S., Leu, N., Bradley, H., Kato, H., Bunting, K., & McLaughlin, K. (2007). Hematopoietic reconstitution with androgenetic and gynogenetic stem cells. Genes and Development, 21(4), 409–419.

    Article  CAS  Google Scholar 

  54. Cavenee, W. (1989). Loss of heterozygosity in stages of malignancy. Clinical Chemistry, 35, B48–B52.

    CAS  Google Scholar 

  55. Lowry, W., Richter, L., Yachechko, R., Pyle, A., Tchieu, J., Sridharan, R., et al. (2008). Generation of human induced pluripotent stem cells from dermal fibroblasts. Proceedings of the National Academy of Sciences of the United States of America, 105(8), 2883–2888.

    Article  CAS  Google Scholar 

  56. Okita, K., Ichisaka, T., & Yamanaka, S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature, 448(7151), 313–317.

    Article  CAS  Google Scholar 

  57. Park, I., Zhao, R., West, J., Yabuuchi, A., Huo, H., Ince, T., et al. (2008). Reprogramming of human somatic cells to pluripotency with defined factors. Nature, 451(7175), 141–146.

    Article  CAS  Google Scholar 

  58. 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.

    Article  CAS  Google Scholar 

  59. 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.

    Article  CAS  Google Scholar 

  60. 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.

    Article  CAS  Google Scholar 

  61. Yu, J., Vodyanik, M., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J., Tian, S., et al. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science, 318(5858), 1917–1920.

    Article  CAS  Google Scholar 

  62. Aoi, T., Yae, K., Nakagawa, M., Ichisaka, T., Okita, K., Takahashi, K., et al. (2008). Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science, 321(5889), 699–702.

    Article  CAS  Google Scholar 

  63. Stadtfeld, M., Brennand, K., & Hochedlinger, K. (2008). Reprogramming of pancreatic beta cells into induced pluripotent stem cells. Current Biology, 18(12), 890–894.

    Article  CAS  Google Scholar 

  64. Hanna, J., Wernig, M., Markoulaki, S., Sun, C., Meissner, A., Cassady, J., et al. (2007). Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science, 318(5858), 1920–1923.

    Article  CAS  Google Scholar 

  65. Dimos, J., Rodolfa, K., Niakan, K., Weisenthal, L., 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.

    Article  CAS  Google Scholar 

  66. Soldner, F., Hockemeyer, D., Beard, C., Gao, Q., Bell, G., Cook, E., et al. (2009). Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell, 136(5), 964–977.

    Article  CAS  Google Scholar 

  67. Zhang, J., Wilson, G., Soerens, A., Koonce, C., Yu, J., Palecek, S., et al. (2009). Functional cardiomyocytes derived from human induced pluripotent stem cells. Circulation Research, 104(4), e30–e41.

    Article  CAS  Google Scholar 

  68. Weintraub, H., Tapscott, S., Davis, R., Thayer, M., Adam, M., Lassar, A., et al. (1989). Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD. Proceedings of the National Academy of Sciences of the United States of America, 86(14), 5434–5438.

    Article  CAS  Google Scholar 

  69. Xie, H., Ye, M., Feng, R., & Graf, T. (2004). Stepwise reprogramming of B cells into macrophages. Cell, 117(5), 663–676.

    Article  CAS  Google Scholar 

  70. Dabeva, M., Hwang, S., Vasa, S., Hurston, E., Novikoff, P., Hixson, D., et al. (1997). Differentiation of pancreatic epithelial progenitor cells into hepaocytes following transplantation into rat liver. Proceedings of the National Academy of Sciences of the United States of America, 94(14), 7356–7361.

    Article  CAS  Google Scholar 

  71. Kojima, H., Fujimiya, M., Matsumura, K., Younan, P., Imaeda, H., Maeda, M., et al. (2003). NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice. Nature Medicine, 9(5), 596–603.

    Article  CAS  Google Scholar 

  72. Zaret, K., & Grompe, M. (2008). Generation and regeneration of cells of the liver and pancreas. Science, 322(5907), 1490–1494.

    Article  CAS  Google Scholar 

  73. Zhou, Q., Brown, J., Kanarek, A., Rajagopal, J., & Melton, D. (2008). In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature, 455(7213), 627–632.

    Article  CAS  Google Scholar 

  74. Vierbuchen, T., Ostermeier, A., Pang, Z., Kokubu, Y., Südhof, T., & Wernig, M. (2010). Direct conversion of fibroblasts to functional neurons by defined factors. Nature. doi: 10.1038/nature08797.

  75. Johansson, T., Westin, G., & Skogseid, B. (2009). Identification of Achaete-scute complex-like 1 (ASCL1) target genes and evaluation of DKK1 and TPH1 expression in pancreatic endocrine tumours. BMC Cancer, 9, 321.

    Article  CAS  Google Scholar 

  76. Goodall, J., Carreira, S., Denat, L., Kobi, D., Davidson, I., Nuciforo, P., et al. (2008). Brn-2 represses microphthalmia-associated transcription factor expression and marks a distinct subpopulation of microphthalmia-associated transcription factor-negative melanoma cells. Cancer Research, 68(19), 7788–7794.

    Article  CAS  Google Scholar 

  77. Vrijenhoek, T., Buizer-Voskamp, J. E., van der Stelt, I., Strengman, E., Genetic Risk and Outcome in Psychosis (GROUP) Consortium, Sabatti, C., et al. (2008). Recurrent CNVs disrupt three candidate genes in schizophrenia patients. American Journal of Human Genetics, 83(4), 504–510.

    Article  CAS  Google Scholar 

  78. Hacein-Bey-Abina, S., Von Kalle, C., Schmidt, M., McCormack, M., Wulffraat, N., Leboulch, P., et al. (2003). LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science, 302(5644), 415–419.

    Article  CAS  Google Scholar 

  79. Dava, S., & Berns, K. (2008). Gene therapy using adeno-associated virus vectors. Clinical Microbiology Reviews, 4, 583–593.

    Google Scholar 

  80. Millington, M., Arndt, A., Boyd, M., Applegate, T., & Shen, S. (2009). Towards a clinically relevant lentiviral transduction protocol for primary human CD34+ hematopoietic stem/progenitor cells. PLoS One, 4(7), e6461.

    Article  CAS  Google Scholar 

  81. Bauer, G., Dao, M., Case, S., Meyerrose, T., Wirthlin, L., Zhou, P., et al. (2008). In vivo safety model to assess the risk of adverse events from retroviral and lentiviral vectors. Molecular Therapy, 16(7), 1308–1315.

    Article  CAS  Google Scholar 

  82. U.S. National Library of Medicine. (December, 2009). Cited January 18, 2010, from www.clinicaltrial.gov.

  83. 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.

    Article  CAS  Google Scholar 

  84. Niwa, H., Miyazaki, J., & Smith, A. (2000). Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nature Genetics, 24(4), 372–376.

    Article  CAS  Google Scholar 

  85. Foster, K., Liu, Z., Nail, C., Li, X., Fitzgerald, T., Bailey, S., et al. (2005). Induction of KLF4 in basal keratinocytes blocks the proliferation-differentiation switch and initiates squamous epithelial dysplasia. Oncogene, 24, 1491–1500.

    Article  CAS  Google Scholar 

  86. Foster, K., Ren, S., Louro, I., Lobo-Ruppert, S., McKie-Bell, P., Grizzle, W., et al. (1999). Oncogene expression cloning by retroviral transduction of adenovirus E1a-immortalized rat kidney RK3E cells: Transformation of a host with epithelial features by c-MYC and the zinc finger protein GKLF. Cell Growth and Differentiation, 10, 423–434.

    CAS  Google Scholar 

  87. 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.

    Article  CAS  Google Scholar 

  88. Stadtfeld, M., Nagaya, M., Utikal, J., Weir, G., & Hochedlinger, K. (2008). Induced pluripotent stem cells generated without viral integration. Science, 322(5903), 945–949.

    Article  CAS  Google Scholar 

  89. Yu, J., Hu, K., Smuga-Otto, K., Tian, S., Stewart, R., Slukvin, I., et al. (2009). Human induced pluripotent stem cells free of vector and transgene sequences. Science, 324(5928), 797–801.

    Article  CAS  Google Scholar 

  90. 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, 771–775.

    Article  CAS  Google Scholar 

  91. Woltjen, K., Michael, I., Mohseni, P., Desai, R., Mileikovsky, M., Hämäläinen, R., et al. (2009). piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature, 458, 766–770.

    Article  CAS  Google Scholar 

  92. Zhao, R., & Daley, G. (2008). From fibroblasts to iPS cells: Induced pluripotency by defined factors. Journal of Cellular Biochemistry, 105(4), 949–955.

    Article  CAS  Google Scholar 

  93. 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.

    Article  CAS  Google Scholar 

  94. Shi, Y., Desponts, C., Do, J., Hahm, H., Schöler, H., & Ding, S. (2008). Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell, 3(5), 568–574.

    Article  CAS  Google Scholar 

  95. Shi, Y., Do, J., Desponts, C., Hahm, H., Schöler, H., & Ding, S. (2008). A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell, 2(6), 525–528.

    Article  CAS  Google Scholar 

  96. Zhou, H., Wu, S., Joo, J., Zhu, S., Han, D., Lin, T., et al. (2009). Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell, 4(5), 381–384.

    Article  CAS  Google Scholar 

  97. Kim, D., Kim, C.-H., Moon, J.-I., Chung, Y.-G., Chang, M.-Y., Han, B.-S., et al. (2009). Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell, 4, 472–476.

    Article  CAS  Google Scholar 

  98. Page, R., Ambady, S., Holmes, W., Vilner, L., Kole, D., Kashpur, O., et al. (2009). Induction of stem cell gene expression in adult human fibroblasts without transgenes. Cloning and Stem Cells, 11(3), 417–426.

    Article  CAS  Google Scholar 

  99. Bird, A. (2002). DNA methylation patterns and epigenetic memory. Genes and Development, 16, 6–21.

    Article  CAS  Google Scholar 

  100. Allegrucci, C., Thurston, A., Lucas, E., & Young, L. (2005). Epigenetics and the germline. Reproduction, 129, 137–149.

    Article  CAS  Google Scholar 

  101. Cox, G., Burger, J., Lip, V., Mau, U., Sperling, K., Wu, B., et al. (2002). Intracytoplasmic sperm injection may increase the risk of imprinting defects. American Journal of Human Genetics, 71(1), 162–164.

    Article  CAS  Google Scholar 

  102. DeBaun, M., Niemitz, E., & Feinberg, A. (2003). Association of in vitro fertilization with Beckwith-Wiedemann Syndrome and epigenetic alterations of LIT1 and H19. American Journal of Human Genetics, 72(1), 156–160.

    Article  CAS  Google Scholar 

  103. Douzgou, S., Mingarelli, R., Tarani, L., De Crescenzo, A., & Riccio, A. (2008). Silver-Russell syndrome following in vitro fertilization. Pediatric and Developmental Pathology, 11(4), 329–331.

    Article  Google Scholar 

  104. Gicquel, C., Gaston, V., Mandelbaum, J., Siffroi, J., Flahault, A., & Le Bouc, Y. (2003). In vitro fertilization may increase the risk of Beckwith-Wiedemann Syndrome related to the abnormal imprinting of the KCNQ1OT gene. American Journal of Human Genetics, 72(5), 1338–1341.

    Article  CAS  Google Scholar 

  105. Kagami, M., Nagai, T., Fukami, M., & Yamazawa, K. O. T. (2007). Silver-Russell syndrome in a girl born after in vitro fertilization: Partial hypermethylation at the differentially methylated region of PEG1/MEST. Journal of Assisted Reproduction and Genetics, 24(4), 131–136.

    Article  Google Scholar 

  106. Maher, E., Afnan, M., & Barratt, C. (2003). Epigenetic risks related to reproductive technologies: Epigenetics, imprinting, ART and icebergs? Human Reproduction, 18(12), 2508–2511.

    Article  Google Scholar 

  107. Maher, E., Brueton, L., Bowdin, S., Luharia, A., Cooper, W., Cole, T., et al. (2003). Beckwith-Wiedemann syndrome and assisted reproduction technology (ART). Journal of Medical Genetics, 40, 62–64.

    Article  CAS  Google Scholar 

  108. Orstavik, K., Eiklid, K., van der Hagen, C., Spetalen, S., Kierulf, K., Skjeldal, O., et al. (2003). Another case of imprinting in a girl with Angelman Syndrome who was conceived by intracytoplasmic sperm injection. American Journal of Human Genetics, 72(1), 218–219.

    Article  CAS  Google Scholar 

  109. Svensson, J., Björnståhl, A., & Ivarsson, S. (2005). Increased risk of Silver-Russell syndrome after in vitro fertilization? Acta Paediatrica, 94(8), 1163–1165.

    Article  Google Scholar 

  110. Laprise, S. (2009). Implications of epigenetics and genomic imprinting in assisted reproductive technologies. Molecular Reproduction & Development, 76(11), 1006–1018.

    Article  CAS  Google Scholar 

  111. Mitalipov, S. (2006). Genomic imprinting in primate embryos and embryonic stem cells. Reproduction, Fertility, and Development, 18(8), 817–821.

    Article  CAS  Google Scholar 

  112. Mitalipov, S., Clepper, L., Sritanaudomchai, H., Fujimoto, A., & Wolf, D. (2007). Methylation status of imprinting centers for H19/IGF2 and SNURF/SNRPN in primate embryonic stem cells. Stem Cells, 25(3), 581–588.

    Article  CAS  Google Scholar 

  113. Kim, K., Thurston, A., Mummery, C., Ward-van Oostwaard, D., Priddle, H., Allegrucci, C., et al. (2007). Gene-specific vulnerability to imprinting variability in human embryonic stem cell lines. Genome Research, 17(12), 1731–1742.

    Article  CAS  Google Scholar 

  114. Rugg-Gunn, P., Ferguson-Smith, A., & Pedersen, R. (2007). Status of genomic imprinting in human embryonic stem cells as revealed by a large cohort of independently derived and maintained lines. Human Molecular Genetics, 16(2), R243–R251.

    Article  CAS  Google Scholar 

  115. Yang, X., Smith, S., Tian, X., Lewin, H., Renard, J., & Wakayama, T. (2007). Nuclear reprogramming of cloned embryos and its implications for therapeutic cloning. Nature Genetics, 39(3), 295–302.

    Article  CAS  Google Scholar 

  116. Armstrong, L., Lako, M., Dean, W., & Stojkovic, M. (2006). Epigenetic modification is central to genome reprogramming in somatic cell nuclear transfer. Stem Cells, 24, 802–814.

    Article  Google Scholar 

  117. Wilmut, I., Schnieke, A., McWhir, J., Kind, A., & Campbell, K. (1997). Viable offspring derived from fetal and adult mammalian cells. Nature, 385(6619), 810–813.

    Article  CAS  Google Scholar 

  118. Gomez, M., Pope, C., Giraldo, A., Lyons, L., Harris, R., King, A., et al. (2004). Birth of African wildcat cloned kittens born from domestic cats. Cloning and Stem Cells, 6(3), 247–258.

    CAS  Google Scholar 

  119. Lanza, R., Cibelli, J., Diaz, F., Moraes, C., Farin, P., Farin, C., et al. (2000). Cloning of an endangered species (Bos gaurus) using interspecies embryo transfer. Cloning, 2, 79–90.

    Article  CAS  Google Scholar 

  120. Cibelli, J., Campbell, K., Seidel, G., West, M., & Lanza, R. (2002). The health profile of cloned animals. Nature Biotechnology, 20(1), 13–14.

    Article  CAS  Google Scholar 

  121. Farin, P., Piedrahita, J., & Farin, C. (2006). Errors in development of fetuses and placentas from in vitro-produced bovine embryos. Theriogenology, 65(1), 178–191.

    Article  Google Scholar 

  122. Palmieri, C., Loi, P., Ptak, G., & Della Salda, L. (2008). Review paper: A review of the pathology of abnormal placentae of somatic cell nuclear transfer clone pregnancies in cattle, sheep, and mice. Veterinary Pathology, 45(6), 865–880.

    Article  CAS  Google Scholar 

  123. Young, L., Sinclair, K., & Wilmut, I. (1998). Large offspring syndrome in cattle and sheep. Reviews of Reproduction, 3, 155–163.

    Article  CAS  Google Scholar 

  124. Mann, M., Lee, S., Doherty, A., Verona, L., Nolen, L., Schultz, R., et al. (2004). Selective loss of imprinting in the placenta following preimplantation development in culture. Development, 131(15), 3727–3735.

    Article  CAS  Google Scholar 

  125. Humpherys, D., Eggen, K., Akutsu, H., Friedman, A., Hochedlinger, K., Yanagimachi, R., et al. (2002). Abnormal gene expression in cloned mice derived from embryonic stem cell and cumulus cell nuclei. Proceedings of the National Academy of Sciences of the United States of America, 99, 12889–12894.

    Article  CAS  Google Scholar 

  126. 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.

    Article  CAS  Google Scholar 

  127. Stem Cell Research. (January 8, 2008). Science and nature 2008. Cited June 29, 2009, from http://www.pollingreport.com/science.htm.

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The author thanks Vikki Rodgers for many helpful comments on the manuscript.

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    Shari L. Laprise

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Laprise, S.L. Progenitor Cells for Regenerative Medicine and Consequences of ART and Cloning-Associated Epimutations. Mol Biotechnol 45, 187–197 (2010). https://doi.org/10.1007/s12033-010-9252-y

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