Stem Cell Reviews and Reports

, Volume 13, Issue 6, pp 757–773 | Cite as

Derivation of Human Induced Pluripotent Stem Cell (iPSC) Lines and Mechanism of Pluripotency: Historical Perspective and Recent Advances

Article

Abstract

Derivation of human embryonic stem cell (hES) lines in 1998 was not only a major technological breakthrough in the field of regenerative medicine; it also triggered a passionate debate about the ethical issues associated with the utilization of human embryos for derivation of hESC lines. Successful derivation of induced pluripotent stem cell (iPS) lines from human somatic cells with defined reprogramming factors by Shinya Yamanaka`s group in 2007 was another breakthrough that generated enormous excitement and hope for the development of donor-specific personalized cell replacement therapies (CRT) without the ethical dilemma associated with it. As we approach twentieth anniversary of derivation of hESC lines and the tenth anniversary of isolation of donor-specific iPSC lines, this manuscript summarizes the key advances in pluripotent stem cell (PSC) research field that led to derivation of human iPSC lines, different methodologies for derivation iPSC lines and characterization of the mechanism of reprogramming. We will also review progress towards generating donor-specific somatic cell lineages from iPSC lines, especially the functional immune cell lineages, and progress towards advancing these findings to the clinic. Finally, we will discuss the challenges, such as genome instability and inherent immunogenicity of hPSC lines that need to be addressed to develop safe and effective iPSC-based CRT.

Keywords

Human embryonic stem cells (hESC) Human pluripotent stem cells (hPS) Induced pluripotent stem cells (iPS). iPSC-based cell replacement therapies (CRT) 

Abbreviations

hPS cells

Human pluripotent stem cells

hES cells

Human embryonic stem cells

iPS cells

Induced pluripotent stem cells

EB

Embryoid bodies

Notes

Acknowledgements

Arvind Chhabra conceived and wrote the manuscript. Arvind Chhabra made the figures, in part using the Servier-Medical Art Slides. Author offers heartfelt gratitude to authors of the manuscripts that are cited here and many more that could not be included because of the space limitations. Author also thanks Deepika Batra and Feny Rasania for help in the preparation of the manuscript. This work was supported by grants from the State of Connecticut Regenerative Medicine Program (10-SCA-23 and 13-SCB-05).

Compliance with Ethical Standards

Conflict of Interest

The author has no financial or otherwise conflict of interest associated with this study to disclose.

References

  1. 1.
    Andrews, P. W. (1988). Human teratocarcinomas. Biochimica et Biophysica Acta, 948, 17–36.PubMedGoogle Scholar
  2. 2.
    Martin, G. R., & Evans, M. J. (1974). The morphology and growth of a pluripotent teratocarcinoma cell line and its derivatives in tissue culture. Cell, 2, 163–172.PubMedCrossRefGoogle Scholar
  3. 3.
    Kleinsmith, L. J., & Pierce, G. B. Jr. (1964). Multipotentiality of single embryonal carcinoma cells. Cancer Research, 24, 1544–1551.PubMedGoogle Scholar
  4. 4.
    Andrews, P. W., Damjanov, I., Simon, D., Banting, G. S., Carlin, C., Dracopoli, N. C., & Fogh, J. (1984). Pluripotent embryonal carcinoma clones derived from the human teratocarcinoma cell line Tera-2. Differentiation in vivo and in vitro. Laboratory Investigation, 50, 147–162.PubMedGoogle Scholar
  5. 5.
    Evans, M. J., & Kaufman, M. H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature, 292, 154–156.PubMedCrossRefGoogle Scholar
  6. 6.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Matsui, Y., Zsebo, K., & Hogan, B. L. (1992). Derivation of pluripotential embryonic stem cells from murine primordial germ cells in culture. Cell, 70, 841–847.PubMedCrossRefGoogle Scholar
  8. 8.
    Resnick, J. L., Bixler, L. S., Cheng, L., & Donovan, P. J. (1992). Long-term proliferation of mouse primordial germ cells in culture. Nature, 359, 550–551.PubMedCrossRefGoogle Scholar
  9. 9.
    Thomson, J. A., Kalishman, J., Golos, T. G., Durning, M., Harris, C. P., Becker, R. A., & Hearn, J. P. (1995). Isolation of a primate embryonic stem cell line. Proceedings of the National Academy of Sciences of the United States of America, 92, 7844–7848.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., & Jones, J. M. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282, 1145–1147.PubMedCrossRefGoogle Scholar
  11. 11.
    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
  12. 12.
    Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131, 861–872.PubMedCrossRefGoogle Scholar
  13. 13.
    Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., Nie, J., Jonsdottir, G. A., Ruotti, V., Stewart, R., Slukvin, I. I., & Thomson, J. A. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science, 318, 1917–1920.PubMedCrossRefGoogle Scholar
  14. 14.
    Wernig, M., Meissner, A., Foreman, R., Brambrink, T., Ku, M., Hochedlinger, K., Bernstein, B. E., & Jaenisch, R. (2007). In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature, 448, 318–324.PubMedCrossRefGoogle Scholar
  15. 15.
    Gurdon, J. B. (1962). The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. Journal of Embryology and Experimental Morphology, 10, 622–640.PubMedGoogle Scholar
  16. 16.
    Campbell, K. H., McWhir, J., Ritchie, W. A., & Wilmut, I. (1996). Sheep cloned by nuclear transfer from a cultured cell line. Nature, 380, 64–66.PubMedCrossRefGoogle Scholar
  17. 17.
    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
  18. 18.
    Munsie, M. J., Michalska, A. E., O’Brien, C. M., Trounson, A. O., Pera, M. F., & Mountford, P. S. (2000). Isolation of pluripotent embryonic stem cells from reprogrammed adult mouse somatic cell nuclei. Current Biology, 10, 989–992.PubMedCrossRefGoogle Scholar
  19. 19.
    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
  20. 20.
    Tachibana, M., Amato, P., Sparman, M., Gutierrez, N. M., Tippner-Hedges, R., Ma, H., Kang, E., Fulati, A., Lee, H. S., Sritanaudomchai, H., Masterson, K., Larson, J., Eaton, D., Sadler-Fredd, K., Battaglia, D., Lee, D., Wu, D., Jensen, J., Patton, P., Gokhale, S., Stouffer, R. L., Wolf, D., & Mitalipov, S. (2013). Human embryonic stem cells derived by somatic cell nuclear transfer. Cell, 153, 1228–1238.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Noggle, S., Fung, H. L., Gore, A., Martinez, H., Satriani, K. C., Prosser, R., Oum, K., Paull, D., Druckenmiller, S., Freeby, M., Greenberg, E., Zhang, K., Goland, R., Sauer, M. V., Leibel, R. L., & Egli, D. (2011). Human oocytes reprogram somatic cells to a pluripotent state. Nature, 478, 70–75.PubMedCrossRefGoogle Scholar
  22. 22.
    French, A. J., Adams, C. A., Anderson, L. S., Kitchen, J. R., Hughes, M. R., & Wood, S. H. (2008). Development of human cloned blastocysts following somatic cell nuclear transfer with adult fibroblasts. Stem Cells, 26, 485–493.PubMedCrossRefGoogle Scholar
  23. 23.
    Fan, Y., Jiang, Y., Chen, X., Ou, Z., Yin, Y., Huang, S., Kou, Z., Li, Q., Long, X., Liu, J., Luo, Y., Liao, B., Gao, S., & Sun, X. (2011). Derivation of cloned human blastocysts by histone deacetylase inhibitor treatment after somatic cell nuclear transfer with beta-thalassemia fibroblasts. Stem Cells and Development, 20, 1951–1959.PubMedCrossRefGoogle Scholar
  24. 24.
    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, 1553–1558.PubMedCrossRefGoogle Scholar
  25. 25.
    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, 1369–1373.PubMedCrossRefGoogle Scholar
  26. 26.
    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, 168–176.PubMedCrossRefGoogle Scholar
  27. 27.
    Nichols, J., Zevnik, B., Anastassiadis, K., Niwa, H., Klewe-Nebenius, D., Chambers, I., Scholer, H., & Smith, A. (1998). Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell, 95, 379–391.PubMedCrossRefGoogle Scholar
  28. 28.
    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, 372–376.PubMedCrossRefGoogle Scholar
  29. 29.
    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, 126–140.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Mitsui, K., Tokuzawa, Y., Itoh, H., Segawa, K., Murakami, M., Takahashi, K., Maruyama, M., Maeda, M., & Yamanaka, S. (2003). The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell, 113, 631–642.PubMedCrossRefGoogle Scholar
  31. 31.
    Niwa, H., Burdon, T., Chambers, I., & Smith, A. (1998). Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3. Genes and Development, 12, 2048–2060.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Matsuda, T., Nakamura, T., Nakao, K., Arai, T., Katsuki, M., Heike, T., & Yokota, T. (1999). STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells. EMBO Journal, 18, 4261–4269.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Takahashi, K., Mitsui, K., & Yamanaka, S. (2003). Role of ERas in promoting tumour-like properties in mouse embryonic stem cells. Nature, 423, 541–545.PubMedCrossRefGoogle Scholar
  34. 34.
    Cartwright, P., McLean, C., Sheppard, A., Rivett, D., Jones, K., & Dalton, S. (2005). LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism. Development, 132, 885–896.PubMedCrossRefGoogle Scholar
  35. 35.
    Li, Y., McClintick, J., Zhong, L., Edenberg, H. J., Yoder, M. C., & Chan, R. J. (2005). Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4. Blood, 105, 635–637.PubMedCrossRefGoogle Scholar
  36. 36.
    Kielman, M. F., Rindapaa, M., Gaspar, C., van Poppel, N., Breukel, C., van Leeuwen, S., Taketo, M. M., Roberts, S., Smits, R., & Fodde, R. (2002). Apc modulates embryonic stem-cell differentiation by controlling the dosage of beta-catenin signaling. Nature Genetics, 32, 594–605.PubMedCrossRefGoogle Scholar
  37. 37.
    Sato, N., Meijer, L., Skaltsounis, L., Greengard, P., & Brivanlou, A. H. (2004). Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Natural Medicines, 10, 55–63.CrossRefGoogle Scholar
  38. 38.
    Maruyama, M., Ichisaka, T., Nakagawa, M., & Yamanaka, S. (2005). Differential roles for Sox15 and Sox2 in transcriptional control in mouse embryonic stem cells. The Journal of Biological Chemistry, 280, 24371–24379.PubMedCrossRefGoogle Scholar
  39. 39.
    Tokuzawa, Y., Kaiho, E., Maruyama, M., Takahashi, K., Mitsui, K., Maeda, M., Niwa, H., & Yamanaka, S. (2003). Fbx15 is a novel target of Oct3/4 but is dispensable for embryonic stem cell self-renewal and mouse development. Molecular and Cellular Biology, 23, 2699–2708.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Sommer, C. A., Stadtfeld, M., Murphy, G. J., Hochedlinger, K., Kotton, D. N., & Mostoslavsky, G. (2009). Induced pluripotent stem cell generation using a single lentiviral stem cell cassette. Stem Cells, 27, 543–549.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Okita, K., Ichisaka, T., & Yamanaka, S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature, 448, 313–317.PubMedCrossRefGoogle Scholar
  42. 42.
    Yusa, K., Rad, R., Takeda, J., & Bradley, A. (2009). Generation of transgene-free induced pluripotent mouse stem cells by the piggyBac transposon. Nature Methods, 6, 363–369.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Woltjen, K., Michael, I. P., Mohseni, P., Desai, R., Mileikovsky, M., Hamalainen, R., Cowling, R., Wang, W., Liu, P., Gertsenstein, M., Kaji, K., Sung, H. K., & Nagy, A. (2009). piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature, 458, 766–770.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Okita, K., Nakagawa, M., Hyenjong, H., Ichisaka, T., & Yamanaka, S. (2008). Generation of mouse induced pluripotent stem cells without viral vectors. Science, 322, 949–953.PubMedCrossRefGoogle Scholar
  46. 46.
    Warren, L., Manos, P. D., Ahfeldt, T., Loh, Y. H., Li, H., Lau, F., Ebina, W., Mandal, P. K., Smith, Z. D., Meissner, A., Daley, G. Q., Brack, A. S., Collins, J. J., Cowan, C., Schlaeger, T. M., & Rossi, D. J. (2010). Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell, 7, 618–630.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Jia, F., Wilson, K. D., Sun, N., Gupta, D. M., Huang, M., Li, Z., Panetta, N. J., Chen, Z. Y., Robbins, R. C., Kay, M. A., Longaker, M. T., & Wu, J. C. (2010). A nonviral minicircle vector for deriving human iPS cells. Nature Methods, 7, 197–199.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Stadtfeld, M., Nagaya, M., Utikal, J., Weir, G., & Hochedlinger, K. (2008). Induced pluripotent stem cells generated without viral integration. Science, 322, 945–949.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Ye, L., Muench, M. O., Fusaki, N., Beyer, A. I., Wang, J., Qi, Z., Yu, J., & Kan, Y. W. (2013). Blood cell-derived induced pluripotent stem cells free of reprogramming factors generated by Sendai viral vectors. Stem Cells Translational Medicine, 2, 558–566.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Chhabra, A., Chen, I. P., & Batra, D. (2017). Human dendritic cell-derived induced pluripotent stem cell lines are not immunogenic. Journal of Immunology, 198, 1875–1886.CrossRefGoogle Scholar
  51. 51.
    Zhou, H., Wu, S., Joo, J. Y., Zhu, S., Han, D. W., Lin, T., Trauger, S., Bien, G., Yao, S., Zhu, Y., Siuzdak, G., Scholer, H. R., Duan, L., & Ding, S. (2009). Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell, 4, 381–384.PubMedCrossRefGoogle Scholar
  52. 52.
    Murchison, E. P., Partridge, J. F., Tam, O. H., Cheloufi, S., & Hannon, G. J. (2005). Characterization of Dicer-deficient murine embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 102, 12135–12140.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Kanellopoulou, C., Muljo, S. A., Kung, A. L., Ganesan, S., Drapkin, R., Jenuwein, T., Livingston, D. M., & Rajewsky, K. (2005). Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes and Development, 19, 489–501.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Houbaviy, H. B., Murray, M. F., & Sharp, P. A. (2003). Embryonic stem cell-specific MicroRNAs. Developmental Cell, 5, 351–358.PubMedCrossRefGoogle Scholar
  55. 55.
    Judson, R. L., Babiarz, J. E., Venere, M., & Blelloch, R. (2009). Embryonic stem cell-specific microRNAs promote induced pluripotency. Nature Biotechnology, 27, 459–461.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Anokye-Danso, F., Trivedi, C. M., Juhr, D., Gupta, M., Cui, Z., Tian, Y., Zhang, Y., Yang, W., Gruber, P. J., Epstein, J. A., & Morrisey, E. E. (2011). Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell, 8, 376–388.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Gruber, A. J., Grandy, W. A., Balwierz, P. J., Dimitrova, Y. A., Pachkov, M., Ciaudo, C., Nimwegen, E., & Zavolan, M. (2014). Embryonic stem cell-specific microRNAs contribute to pluripotency by inhibiting regulators of multiple differentiation pathways. Nucleic Acids Research, 42, 9313–9326.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Kishigami, S., Mizutani, E., Ohta, H., Hikichi, T., Thuan, N. V., Wakayama, S., Bui, H. T., & Wakayama, T. (2006). Significant improvement of mouse cloning technique by treatment with trichostatin A after somatic nuclear transfer. Biochemical and Biophysical Research Communications, 340, 183–189.PubMedCrossRefGoogle Scholar
  59. 59.
    Rybouchkin, A., Kato, Y., & Tsunoda, Y. (2006). Role of histone acetylation in reprogramming of somatic nuclei following nuclear transfer. Biology of Reproduction, 74, 1083–1089.PubMedCrossRefGoogle Scholar
  60. 60.
    Blelloch, R., Wang, Z., Meissner, A., Pollard, S., Smith, A., & Jaenisch, R. (2006). Reprogramming efficiency following somatic cell nuclear transfer is influenced by the differentiation and methylation state of the donor nucleus. Stem Cells, 24, 2007–2013.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Kim, J. B., Zaehres, H., Wu, G., Gentile, L., Ko, K., Sebastiano, V., Arauzo-Bravo, M. J., Ruau, D., Han, D. W., Zenke, M., & Scholer, H. R. (2008). Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature, 454, 646–650.PubMedCrossRefGoogle Scholar
  62. 62.
    Shi, Y., Do, J. T., Desponts, C., Hahm, H. S., Scholer, H. R., & Ding, S. (2008). A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell, 2, 525–528.PubMedCrossRefGoogle Scholar
  63. 63.
    Feldman, N., Gerson, A., Fang, J., Li, E., Zhang, Y., Shinkai, Y., Cedar, H., & Bergman, Y. (2006). G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis. Nature Cell Biology, 8, 188–194.PubMedCrossRefGoogle Scholar
  64. 64.
    Shi, Y., Desponts, C., Do, J. T., Hahm, H. S., Scholer, H. R., & Ding, S. (2008). Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell, 3, 568–574.PubMedCrossRefGoogle Scholar
  65. 65.
    Huangfu, D., Maehr, R., Guo, W., Eijkelenboom, A., Snitow, M., Chen, A. E., & Melton, D. A. (2008). Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nature Biotechnology, 26, 795–797.PubMedCrossRefGoogle Scholar
  66. 66.
    O’Connor, M. D., Kardel, M. D., Iosfina, I., Youssef, D., Lu, M., Li, M. M., Vercauteren, S., Nagy, A., & Eaves, C. J. (2008). Alkaline phosphatase-positive colony formation is a sensitive, specific, and quantitative indicator of undifferentiated human embryonic stem cells. Stem Cells, 26, 1109–1116.PubMedCrossRefGoogle Scholar
  67. 67.
    Stefkova, K., Prochazkova, J., & Pachernik, J. (2015). Alkaline phosphatase in stem cells. Stem Cells International, 2015, 628368.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    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
  69. 69.
    Pesce, M., & Scholer, H. R. (2001). Oct-4: gatekeeper in the beginnings of mammalian development. Stem Cells, 19, 271–278.PubMedCrossRefGoogle Scholar
  70. 70.
    Niwa, H. (2007). How is pluripotency determined and maintained? Development, 134, 635–646.PubMedCrossRefGoogle Scholar
  71. 71.
    Boyer, L. A., Lee, T. I., Cole, M. F., Johnstone, S. E., Levine, S. S., Zucker, J. P., Guenther, M. G., Kumar, R. M., Murray, H. L., Jenner, R. G., Gifford, D. K., Melton, D. A., Jaenisch, R., & Young, R. A. (2005). Core transcriptional regulatory circuitry in human embryonic stem cells. Cell, 122, 947–956.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Masui, S., Nakatake, Y., Toyooka, Y., Shimosato, D., Yagi, R., Takahashi, K., Okochi, H., Okuda, A., Matoba, R., Sharov, A. A., Ko, M. S., & Niwa, H. (2007). Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nature Cell Biology, 9, 625–635.PubMedCrossRefGoogle Scholar
  73. 73.
    Dang, D. T., Pevsner, J., & Yang, V. W. (2000). The biology of the mammalian Kruppel-like family of transcription factors. The International Journal of Biochemistry & Cell Biology, 32, 1103–1121.CrossRefGoogle Scholar
  74. 74.
    Segre, J. A., Bauer, C., & Fuchs, E. (1999). Klf4 is a transcription factor required for establishing the barrier function of the skin. Nature Genetics, 22, 356–360.PubMedCrossRefGoogle Scholar
  75. 75.
    Zhang, P., Andrianakos, R., Yang, Y., Liu, C., & Lu, W. (2010). Kruppel-like factor 4 (Klf4) prevents embryonic stem (ES) cell differentiation by regulating Nanog gene expression. The Journal of Biological Chemistry, 285, 9180–9189.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Jiang, J., Chan, Y. S., Loh, Y. H., Cai, J., Tong, G. Q., Lim, C. A., Robson, P., Zhong, S., & Ng, H. H. (2008). A core Klf circuitry regulates self-renewal of embryonic stem cells. Nature Cell Biology, 10, 353–360.PubMedCrossRefGoogle Scholar
  77. 77.
    Dang, C. V., O’Donnell, K. A., Zeller, K. I., Nguyen, T., Osthus, R. C., & Li, F. (2006). The c-Myc target gene network. Seminars in Cancer Biology, 16, 253–264.PubMedCrossRefGoogle Scholar
  78. 78.
    Chang, T. C., Yu, D., Lee, Y. S., Wentzel, E. A., Arking, D. E., West, K. M., Dang, C. V., Thomas-Tikhonenko, A., & Mendell, J. T. (2008). Widespread microRNA repression by Myc contributes to tumorigenesis. Nature Genetics, 40, 43–50.PubMedCrossRefGoogle Scholar
  79. 79.
    Knoepfler, P. S., Zhang, X. Y., Cheng, P. F., Gafken, P. R., McMahon, S. B., & Eisenman, R. N. (2006). Myc influences global chromatin structure. EMBO Journal, 25, 2723–2734.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Varlakhanova, N. V., Cotterman, R. F., deVries, W. N., Morgan, J., Donahue, L. R., Murray, S., Knowles, B. B., & Knoepfler, P. S. (2010). myc maintains embryonic stem cell pluripotency and self-renewal. Differentiation, 80, 9–19.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Chambers, I., Colby, D., Robertson, M., Nichols, J., Lee, S., Tweedie, S., & Smith, A. (2003). Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell, 113, 643–655.PubMedCrossRefGoogle Scholar
  82. 82.
    Hyslop, L., Stojkovic, M., Armstrong, L., Walter, T., Stojkovic, P., Przyborski, S., Herbert, M., Murdoch, A., Strachan, T., & Lako, M. (2005). Downregulation of NANOG induces differentiation of human embryonic stem cells to extraembryonic lineages. Stem Cells, 23, 1035–1043.PubMedCrossRefGoogle Scholar
  83. 83.
    Moss, E. G., & Tang, L. (2003). Conservation of the heterochronic regulator Lin-28, its developmental expression and microRNA complementary sites. Developmental Biology, 258, 432–642.PubMedCrossRefGoogle Scholar
  84. 84.
    Balzer, E., & Moss, E. G. (2007). Localization of the developmental timing regulator Lin28 to mRNP complexes, P-bodies and stress granules. RNA Biology, 4, 16–25.PubMedCrossRefGoogle Scholar
  85. 85.
    Scheper, W., & Copray, S. (2009). The molecular mechanism of induced pluripotency: a two-stage switch. Stem Cell Reviews, 5, 204–223.PubMedCrossRefGoogle Scholar
  86. 86.
    Xu, R. H., Chen, X., Li, D. S., Li, R., Addicks, G. C., Glennon, C., Zwaka, T. P., & Thomson, J. A. (2002). BMP4 initiates human embryonic stem cell differentiation to trophoblast. Nature Biotechnology, 20, 1261–1264.PubMedCrossRefGoogle Scholar
  87. 87.
    Qi, X., Li, T. G., Hao, J., Hu, J., Wang, J., Simmons, H., Miura, S., Mishina, Y., & Zhao, G. Q. (2004). BMP4 supports self-renewal of embryonic stem cells by inhibiting mitogen-activated protein kinase pathways. Proceedings of the National Academy of Sciences of the United States of America, 101, 6027–6032.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Meshorer, E., Yellajoshula, D., George, E., Scambler, P. J., Brown, D. T., & Misteli, T. (2006). Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Developmental Cell, 10, 105–116.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Bernstein, B. E., Mikkelsen, T. S., Xie, X., Kamal, M., Huebert, D. J., Cuff, J., Fry, B., Meissner, A., Wernig, M., Plath, K., Jaenisch, R., Wagschal, A., Feil, R., Schreiber, S. L., & Lander, E. S. (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell, 125, 315–326.PubMedCrossRefGoogle Scholar
  90. 90.
    Azuara, V., Perry, P., Sauer, S., Spivakov, M., Jorgensen, H. F., John, R. M., Gouti, M., Casanova, M., Warnes, G., Merkenschlager, M., & Fisher, A. G. (2006). Chromatin signatures of pluripotent cell lines. Nature Cell Biology, 8, 532–538.PubMedCrossRefGoogle Scholar
  91. 91.
    Nazor, K. L., Altun, G., Lynch, C., Tran, H., Harness, J. V., Slavin, I., Garitaonandia, I., Muller, F. J., Wang, Y. C., Boscolo, F. S., Fakunle, E., Dumevska, B., Lee, S., Park, H. S., Olee, T., D’Lima, D. D., Semechkin, R., Parast, M. M., Galat, V., Laslett, A. L., Schmidt, U., Keirstead, H. S., Loring, J. F., & Laurent, L. C. (2012). Recurrent variations in DNA methylation in human pluripotent stem cells and their differentiated derivatives. Cell Stem Cell, 10, 620–634.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Lee, T. I., Jenner, R. G., Boyer, L. A., Guenther, M. G., Levine, S. S., Kumar, R. M., Chevalier, B., Johnstone, S. E., Cole, M. F., Isono, K., Koseki, H., Fuchikami, T., Abe, K., Murray, H. L., Zucker, J. P., Yuan, B., Bell, G. W., Herbolsheimer, E., Hannett, N. M., Sun, K., Odom, D. T., Otte, A. P., Volkert, T. L., Bartel, D. P., Melton, D. A., Gifford, D. K., Jaenisch, R., & Young, R. A. (2006). Control of developmental regulators by Polycomb in human embryonic stem cells. Cell, 125, 301–313.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Kim, K., Doi, A., Wen, B., Ng, K., Zhao, R., Cahan, P., Kim, J., Aryee, M. J., Ji, H., Ehrlich, L. I., Yabuuchi, A., Takeuchi, A., Cunniff, K. C., Hongguang, H., McKinney-Freeman, S., Naveiras, O., Yoon, T. J., Irizarry, R. A., Jung, N., Seita, J., Hanna, J., Murakami, P., Jaenisch, R., Weissleder, R., Orkin, S. H., Weissman, I. L., Feinberg, A. P., & Daley, G. Q. (2010). Epigenetic memory in induced pluripotent stem cells. Nature, 467, 285–290.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Vaskova, E. A., Stekleneva, A. E., Medvedev, S. P., & Zakian, S. M. (2013). “Epigenetic memory” phenomenon in induced pluripotent stem cells. Acta Naturae, 5, 15–21.PubMedPubMedCentralGoogle Scholar
  95. 95.
    Shi, Y., Inoue, H., Wu, J. C., & Yamanaka, S. (2017). Induced pluripotent stem cell technology: a decade of progress. Nature Reviews. Drug Discovery, 16, 115–130.PubMedCrossRefGoogle Scholar
  96. 96.
    Zhan, X., Dravid, G., Ye, Z., Hammond, H., Shamblott, M., Gearhart, J., & Cheng, L. (2004). Functional antigen-presenting leucocytes derived from human embryonic stem cells in vitro. Lancet, 364, 163–171.PubMedCrossRefGoogle Scholar
  97. 97.
    Chhabra, A. (2009). MHC class I TCR engineered anti-tumor CD4 T cells: implications for cancer immunotherapy. Endocrine, Metabolic & Immune Disorders Drug Targets, 9, 344–352.CrossRefGoogle Scholar
  98. 98.
    Chhabra, A. (2011). TCR-engineered, customized, antitumor T cells for cancer immunotherapy: advantages and limitations. TheScientificWorldJournal, 11, 121–129.PubMedCrossRefGoogle Scholar
  99. 99.
    Morgan, R. A., Dudley, M. E., Wunderlich, J. R., Hughes, M. S., Yang, J. C., Sherry, R. M., Royal, R. E., Topalian, S. L., Kammula, U. S., Restifo, N. P., Zheng, Z., Nahvi, A., de Vries, C. R., Rogers-Freezer, L. J., Mavroukakis, S. A., & Rosenberg, S. A. (2006). Cancer regression in patients after transfer of genetically engineered lymphocytes. Science, 314, 126–129.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Kalos, M., Levine, B. L., Porter, D. L., Katz, S., Grupp, S. A., Bagg, A., & June, C. H. (2011). T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Science Translational Medicine, 3, 95ra73.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Porter, D. L., Kalos, M., Zheng, Z., Levine, B., & June, C. (2011). Chimeric antigen receptor therapy for b-cell malignancies. Journal of Cancer, 2, 331–332.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Galic, Z., Kitchen, S. G., Kacena, A., Subramanian, A., Burke, B., Cortado, R., & Zack, J. A. (2006). T lineage differentiation from human embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 103, 11742–11747.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Themeli, M., Kloss, C. C., Ciriello, G., Fedorov, V. D., Perna, F., Gonen, M., & Sadelain, M. (2013). Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy. Nature Biotechnology, 31, 928–933.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Nishimura, T., Kaneko, S., Kawana-Tachikawa, A., Tajima, Y., Goto, H., Zhu, D., Nakayama-Hosoya, K., Iriguchi, S., Uemura, Y., Shimizu, T., Takayama, N., Yamada, D., Nishimura, K., Ohtaka, M., Watanabe, N., Takahashi, S., Iwamoto, A., Koseki, H., Nakanishi, M., Eto, K., & Nakauchi, H. (2013). Generation of rejuvenated antigen-specific T cells by reprogramming to pluripotency and redifferentiation. Cell Stem Cell, 12, 114–126.PubMedCrossRefGoogle Scholar
  105. 105.
    Vizcardo, R., Masuda, K., Yamada, D., Ikawa, T., Shimizu, K., Fujii, S., Koseki, H., & Kawamoto, H. (2013). Regeneration of human tumor antigen-specific T cells from iPSCs derived from mature CD8(+) T cells. Cell Stem Cell, 12, 31–36.PubMedCrossRefGoogle Scholar
  106. 106.
    Knorr, D. A., & Kaufman, D. S. (2010). Pluripotent stem cell-derived natural killer cells for cancer therapy. Translational Research, 156, 147–154.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Eguizabal, C., Zenarruzabeitia, O., Monge, J., Santos, S., Vesga, M. A., Maruri, N., Arrieta, A., Rinon, M., Tamayo-Orbegozo, E., Amo, L., Larrucea, S., & Borrego, F. (2014). Natural killer cells for cancer immunotherapy: pluripotent stem cells-derived NK cells as an immunotherapeutic perspective. Frontiers in Immunology, 5, 439.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Becker, P. S., Suck, G., Nowakowska, P., Ullrich, E., Seifried, E., Bader, P., Tonn, T., & Seidl, C. (2016). Selection and expansion of natural killer cells for NK cell-based immunotherapy. Cancer Immunology, Immunotherapy, 65, 477–484.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Vodyanik, M. A., Bork, J. A., Thomson, J. A., & Slukvin, I. I. (2005). Human embryonic stem cell-derived CD34 + cells: efficient production in the coculture with OP9 stromal cells and analysis of lymphohematopoietic potential. Blood, 105, 617–626.PubMedCrossRefGoogle Scholar
  110. 110.
    Woll, P. S., Martin, C. H., Miller, J. S., & Kaufman, D. S. (2005). Human embryonic stem cell-derived NK cells acquire functional receptors and cytolytic activity. Journal of Immunology, 175, 5095–5103.CrossRefGoogle Scholar
  111. 111.
    Woll, P. S., Grzywacz, B., Tian, X., Marcus, R. K., Knorr, D. A., Verneris, M. R., & Kaufman, D. S. (2009). Human embryonic stem cells differentiate into a homogeneous population of natural killer cells with potent in vivo antitumor activity. Blood, 113, 6094–6101.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Feng, Q., Shabrani, N., Thon, J. N., Huo, H., Thiel, A., Machlus, K. R., Kim, K., Brooks, J., Li, F., Luo, C., Kimbrel, E. A., Wang, J., Kim, K. S., Italiano, J., Cho, J., Lu, S. J., & Lanza, R. (2014). Scalable generation of universal platelets from human induced pluripotent stem cells. Stem Cell Reports, 3, 817–831.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Nakamura, S., Takayama, N., Hirata, S., Seo, H., Endo, H., Ochi, K., Fujita, K., Koike, T., Harimoto, K., Dohda, T., Watanabe, A., Okita, K., Takahashi, N., Sawaguchi, A., Yamanaka, S., Nakauchi, H., Nishimura, S., & Eto, K. (2014). Expandable megakaryocyte cell lines enable clinically applicable generation of platelets from human induced pluripotent stem cells. Cell Stem Cell, 14, 535–548.PubMedCrossRefGoogle Scholar
  114. 114.
    Moreau, T., Evans, A. L., Vasquez, L., Tijssen, M. R., Yan, Y., Trotter, M. W., Howard, D., Colzani, M., Arumugam, M., Wu, W. H., Dalby, A., Lampela, R., Bouet, G., Hobbs, C. M., Pask, D. C., Payne, H., Ponomaryov, T., Brill, A., Soranzo, N., Ouwehand, W. H., Pedersen, R. A., & Ghevaert, C. (2016). Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming. Nature Communications, 7, 11208.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Pulecio, J., Alejo-Valle, O., Capellera-Garcia, S., Vitaloni, M., Rio, P., Mejia-Ramirez, E., Caserta, I., Bueren, J. A., Flygare, J., & Raya, A. (2016). Direct conversion of fibroblasts to megakaryocyte progenitors. Cell Reports, 17, 671–683.PubMedCrossRefGoogle Scholar
  116. 116.
    Ilic, D., Devito, L., Miere, C., & Codognotto, S. (2015). Human embryonic and induced pluripotent stem cells in clinical trials. British Medical Bulletin, 116, 19–27.PubMedGoogle Scholar
  117. 117.
    Kimbrel, E. A., & Lanza, R. (2015) Current status of pluripotent stem cells: moving the first therapies to the clinic. Nature Reviews. Drug Discovery, 14, 681–692.PubMedCrossRefGoogle Scholar
  118. 118.
    Schwartz, S. D., Regillo, C. D., Lam, B. L., Eliott, D., Rosenfeld, P. J., Gregori, N. Z., Hubschman, J. P., Davis, J. L., Heilwell, G., Spirn, M., Maguire, J., Gay, R., Bateman, J., Ostrick, R. M., Morris, D., Vincent, M., Anglade, E., Del Priore, L. V., & Lanza, R. (2015). Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy: follow-up of two open-label phase 1/2 studies. Lancet, 385, 509–516.PubMedCrossRefGoogle Scholar
  119. 119.
    Schwartz, S. D., Hubschman, J. P., Heilwell, G., Franco-Cardenas, V., Pan, C. K., Ostrick, R. M., Mickunas, E., Gay, R., Klimanskaya, I., & Lanza, R. (2012). Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet, 379, 713–720.PubMedCrossRefGoogle Scholar
  120. 120.
    D’Amour, K. A., Bang, A. G., Eliazer, S., Kelly, O. G., Agulnick, A. D., Smart, N. G., Moorman, M. A., Kroon, E., Carpenter, M. K., & Baetge, E. E. (2006). Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nature Biotechnology, 24, 1392–1401.PubMedCrossRefGoogle Scholar
  121. 121.
    Jang, J., Yoo, J. E., Lee, J. A., Lee, D. R., Kim, J. Y., Huh, Y. J., Kim, D. S., Park, C. Y., Hwang, D. Y., Kim, H. S., Kang, H. C., & Kim, D. W. (2012). Disease-specific induced pluripotent stem cells: a platform for human disease modeling and drug discovery. Experimental & Molecular Medicine, 44, 202–213.Google Scholar
  122. 122.
    Hoing, S., Rudhard, Y., Reinhardt, P., Glatza, M., Stehling, M., Wu, G., Peiker, C., Bocker, A., Parga, J. A., Bunk, E., Schwamborn, J. C., Slack, M., Sterneckert, J., & Scholer, H. R. (2012). Discovery of inhibitors of microglial neurotoxicity acting through multiple mechanisms using a stem-cell-based phenotypic assay. Cell Stem Cell, 11, 620–632.PubMedCrossRefGoogle Scholar
  123. 123.
    Egawa, N., Kitaoka, S., Tsukita, K., Naitoh, M., Takahashi, K., Yamamoto, T., Adachi, F., Kondo, T., Okita, K., Asaka, I., Aoi, T., Watanabe, A., Yamada, Y., Morizane, A., Takahashi, J., Ayaki, T., Ito, H., Yoshikawa, K., Yamawaki, S., Suzuki, S., Watanabe, D., Hioki, H., Kaneko, T., Makioka, K., Okamoto, K., Takuma, H., Tamaoka, A., Hasegawa, K., Nonaka, T., Hasegawa, M., Kawata, A., Yoshida, M., Nakahata, T., Takahashi, R., Marchetto, M. C., Gage, F. H., Yamanaka, S., & Inoue, H. (2012). Drug screening for ALS using patient-specific induced pluripotent stem cells. Science Translational Medicine, 4, 145ra104.PubMedCrossRefGoogle Scholar
  124. 124.
    Martin, M. J., Muotri, A., Gage, F., & Varki, A. (2005). Human embryonic stem cells express an immunogenic nonhuman sialic acid. Natural Medicines, 11, 228–232.CrossRefGoogle Scholar
  125. 125.
    Desai, N., Rambhia, P., & Gishto, A. (2015). Human embryonic stem cell cultivation: historical perspective and evolution of xeno-free culture systems. Reproductive Biology and Endocrinology, 13, 9.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Zhao, T., Zhang, Z. N., Rong, Z., & Xu, Y. (2011). Immunogenicity of induced pluripotent stem cells. Nature, 474, 212–215.PubMedCrossRefGoogle Scholar
  127. 127.
    Guha, P., Morgan, J. W., Mostoslavsky, G., Rodrigues, N. P., & Boyd, A. S. (2013). Lack of immune response to differentiated cells derived from syngeneic induced pluripotent stem cells. Cell Stem Cell, 12, 407–412.PubMedCrossRefGoogle Scholar
  128. 128.
    Araki, R., Uda, M., Hoki, Y., Sunayama, M., Nakamura, M., Ando, S., Sugiura, M., Ideno, H., Shimada, A., Nifuji, A., & Abe, M. (2013). Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells. Nature, 494, 100–104.PubMedCrossRefGoogle Scholar
  129. 129.
    Chhabra, A. (2017). Inherent immunogenicity or lack thereof of pluripotent stem cells: implications for cell replacement therapy. Frontiers in Immunology, 8, 993.Google Scholar

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© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of MedicineUniversity of Connecticut Health Center (UConn Health)FarmingtonUSA

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