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Genetic Modification of Human Embryonic and Induced Pluripotent Stem Cells: Viral and Non-viral Approaches

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Abstract

Human embryonic stem cells (hESCs) and induced pluripotent cells (iPSCs) are well suited for translational cell therapy. For hESC, the pluripotent phenotype, naturally occurring within the inner cell mass of the early embryo, bestows the capability to differentiate into any cell type of interest and this, coupled with their ability to remain in an undifferentiated state with indefinite proliferative capacity, means that essentially unlimited numbers of identical, well-defined and genetically characterised stem cells can be produced in culture for therapeutic applications. An understanding of the regulatory mechanisms responsible for pluripotency and differentiation potential of hESCs is critical for translating their potential in vitro to therapeutic use in vivo. Harnessing of this therapeutic potential in conjunction with modern genetic modification tools promises great advancement in the study of developmental and adult physiology and pathophysiology with a view towards implementation of genetically modified hESCs to advance regenerative medicine.

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References

  1. Rovira M, Jane-Valbuena J, Marchand M, Savatier P, Real FX, Skoudy A. Viral-mediated coexpression of Pdx1 and p48 regulates exocrine pancreatic differentiation in mouse ES cells. Cloning Stem Cells. Fall 2007; 9(3):327–338.

    Article  Google Scholar 

  2. Li Z, Suzuki Y, Huang M, et al. Comparison of reporter gene and iron particle labeling for tracking fate of human embryonic stem cells and differentiated endothelial cells in living subjects. Stem Cells. 2009 Mar: 18(2):205–14.

    Article  Google Scholar 

  3. Xie X, Chan KS, Cao F, et al. Imaging of STAT3 signaling pathway during mouse embryonic stem cell differentiation. Stem Cells Dev. 2008 Jun 24.

    Google Scholar 

  4. Cao F, Drukker M, Lin S, et al. Molecular imaging of embryonic stem cell misbehavior and suicide gene ablation. Cloning Stem Cells. Spring 2007; 9(1):107–117.

    Article  Google Scholar 

  5. Strulovici Y, Leopold PL, O‘Connor TP, Pergolizzi RG, Crystal RG. Human embryonic stem cells and gene therapy. Mol Ther. 2007 May; 15(5):850–866.

    Google Scholar 

  6. Yu J, Vodyanik M, Smuga-Otto K, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007 Dec 21; 318(5858):1917–20.

    Google Scholar 

  7. Lowry WE, Richter L, Yachechko R, et al. Generation of human induced pluripotent stem cells from dermal fibroblasts. Proc Natl Acad Sci U S A. 2008 Feb 26; 105(8):2883–2888.

    Article  Google Scholar 

  8. Park IH, Zhao R, West JA, et al. Reprogramming of human somatic cells to pluripotency with defined factors. Nature. 2008 Jan 10; 451(7175):141–146.

    Article  Google Scholar 

  9. Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007 Nov 30; 131(5):861–872.

    Article  Google Scholar 

  10. Park IH, Arora N, Huo H, et al. Disease-specific induced pluripotent stem cells. Cell. 2008 Sep 5; 134(5):877–86.

    Article  Google Scholar 

  11. Park IH, Lerou PH, Zhao R, Huo H, Daley GQ. Generation of human-induced pluripotent stem cells. Nat Protoc. 2008; 3(7):1180–1186.

    Article  Google Scholar 

  12. Gao X, Kim KS, Liu D. Nonviral gene delivery: what we know and what is next. Aaps J. 2007; 9(1):E92–E104.

    Article  Google Scholar 

  13. Lakshmipathy U, Pelacho B, Sudo K, et al. Efficient transfection of embryonic and adult stem cells. Stem Cells. 2004; 22(4):531–543.

    Article  Google Scholar 

  14. Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998 Nov 6; 282(5391):1145–1147.

    Article  Google Scholar 

  15. Liew CG, Draper JS, Walsh J, Moore H, Andrews PW. Transient and stable transgene expression in human embryonic stem cells. Stem Cells. 2007 Jun; 25(6):1521–1528.

    Article  Google Scholar 

  16. Eiges R, Schuldiner M, Drukker M, Yanuka O, Itskovitz-Eldor J, Benvenisty N. Establishment of human embryonic stem cell-transfected clones carrying a marker for undifferentiated cells. Curr Biol. 2001 Apr 3; 11(7):514–518.

    Article  Google Scholar 

  17. Lebkowski JS, Gold J, Xu C, Funk W, Chiu CP, Carpenter MK. Human embryonic stem cells: culture, differentiation, and genetic modification for regenerative medicine applications. Cancer J. 2001 Nov-Dec ; 7(Suppl 2):S83–S93.

    Google Scholar 

  18. Siemen H, Nix M, Endl E, Koch P, Itskovitz-Eldor J, Brustle O. Nucleofection of human embryonic stem cells. Stem Cells Dev. 2005 Aug; 14(4):378–383.

    Article  Google Scholar 

  19. Vallier L, Rugg-Gunn PJ, Bouhon IA, Andersson FK, Sadler AJ, Pedersen RA. Enhancing and diminishing gene function in human embryonic stem cells. Stem Cells. 2004; 22(1):2–11.

    Article  Google Scholar 

  20. Zwaka TP, Thomson JA. Homologous recombination in human embryonic stem cells. Nat Biotechnol. 2003 Mar; 21(3):319–321.

    Article  Google Scholar 

  21. Giudice A, Trounson A. Genetic modification of human embryonic stem cells for derivation of target cells. Cell Stem Cell. 2008 May 8; 2(5):422–433.

    Article  Google Scholar 

  22. Anderson D, Self T, Mellor IR, Goh G, Hill SJ, Denning C. Transgenic enrichment of cardiomyocytes from human embryonic stem cells. Mol Ther. 2007 Nov: 15(11):2027–36.

    Article  Google Scholar 

  23. Braam SR, Denning C, van den Brink S, et al. Improved genetic manipulation of human embryonic stem cells. Nat Methods. 2008 May; 5(5):389–392.

    Article  Google Scholar 

  24. Denning C, Allegrucci C, Priddle H, et al. Common culture conditions for maintenance and cardiomyocyte differentiation of the human embryonic stem cell lines, BG01 and HUES-7. Int J Dev Biol. 2006; 50(1):27–37.

    Article  Google Scholar 

  25. Huber I, Itzhaki I, Caspi O, et al. Identification and selection of cardiomyocytes during human embryonic stem cell differentiation. FASEB J. 2007 Aug; 21(10):2551–2563.

    Article  Google Scholar 

  26. Wang D, Haviland DL, Burns AR, Zsigmond E, Wetsel RA. A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells. Proc Natl Acad Sci U S A. 2007 Mar 13; 104(11):4449–4454.

    Article  Google Scholar 

  27. Urbach A, Schuldiner M, Benvenisty N. Modeling for Lesch-Nyhan disease by gene targeting in human embryonic stem cells. Stem Cells. 2004; 22(4):635–641.

    Article  Google Scholar 

  28. Davis RP, Ng ES, Costa M, et al. Targeting a GFP reporter gene to the MIXL1 locus of human embryonic stem cells identifies human primitive streak-like cells and enables isolation of primitive hematopoietic precursors. Blood. 2008 Feb 15; 111(4):1876–1884.

    Article  Google Scholar 

  29. Thyagarajan B, Liu Y, Shin S, et al. Creation of engineered human embryonic stem cell lines using phiC31 integrase. Stem Cells. 2008 Jan ; 26(1):119–126.

    Article  Google Scholar 

  30. Bergelson JM, Cunningham JA, Droguett G, et al. Isolation of a common receptor for coxsackie B viruses and adenoviruses 2 and 5. Science. 1997; 275:1320–1323.

    Article  Google Scholar 

  31. Tomko RP, Xu R, Philipson L. HCAR and MCAR: the human and mouse cellular receptors for subgroup C adenoviruses and group B coxsackieviruses. Proc Nat Acad Sci USA. 1997; 94:3352–3356.

    Article  Google Scholar 

  32. Wickham TJ, Mathias P, Cheresh DA, Nemerow GR. Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. Cell. 1993 Apr 23; 73(2):309–319.

    Article  Google Scholar 

  33. Cohen CJ, Shieh JTC, Pickles RJ, Okegawa T, Hsieh J-T, Bergelson JM. The coxsackievirus and adenovirus receptor is a transmembrane component of the tight junction. PNAS. 2001 Dec 18; 98(26):15191–15196.

    Article  Google Scholar 

  34. Waddington S, McVey J, Bhella D, et al. Adenovirus serotype 5 Hexon mediates liver gene transfer. Cell. 2008; 132(3):397–409.

    Article  Google Scholar 

  35. Kalyuzhniy O, Di Paolo NC, Silvestry M, et al. Adenovirus serotype 5 hexon is critical for virus infection of hepatocytes in vivo. PNAS. 2008; 105(14):5483–5488.

    Article  Google Scholar 

  36. Gaggar A, Shayakhmetov DM, Lieber A. CD46 is a cellular receptor for group B adenoviruses. Nat Med. 2003 Nov; 9(11):1408–1412.

    Article  Google Scholar 

  37. Gaggar A, Shayakhmetov DM, Liszewski MK, Atkinson JP, Lieber A. Localization of regions in CD46 that interact with adenovirus. Virology. 2005; 79:7503–7513.

    Article  Google Scholar 

  38. Tuve S, Wang H, Ware C, et al. A new Group B adenovirus receptor is expressed at high levels on human stem and tumor cells. Virology. 2006 Oct 04; 80(24):12109–12120.

    Article  Google Scholar 

  39. Krasnykh V, Dmitriev I, Mikheeva G, Miller R, Belousova N, Curiel DT. Characterisation of an adenovirus vector containing a heterologous peptide epitope in the HI loop of the fiber knob. J Virol. 1998; 72(3):1844–1852.

    Google Scholar 

  40. Dmitriev I, Krasnykh V, Miller CR, et al. An adenovirus vector with genetically modified fibers demonstrates expanded tropism via utilization of a coxsackievirus and adenovirus receptor-independent cell entry mechanism. J Virol. 1998; 72(12):9706–9713.

    Google Scholar 

  41. Nicklin S, Von Seggern D, Work L, et al. Ablating adenovirus type 5 fiber-CAR binding and HI loop insertion of the SIGYPLP peptide generate an endothelial cell-selective adenovirus. Mol Ther. 2001; 4:534–542.

    Article  Google Scholar 

  42. Nicklin S, White S, Watkins S, Hawkins R, Baker A. Selective targeting of gene transfer to vascular endothelial cells by use of peptides isolated by phage display. Circulation. 2000; 102:231–237.

    Article  Google Scholar 

  43. Pasqualini R, Ruoslahti E. Organ targeting in vivo using phage display peptide libraries. Nature. 1996; 380:364–366.

    Article  Google Scholar 

  44. Cavazzana-C M, Hacein-Bey S, Saint-Basile CD, et al. Gene therapy of human severe combined immunodeficiency (scid)-1x disease. Science. 2000; 288:669–672.

    Article  Google Scholar 

  45. Hacein-Bey-Abina S, Kalle CV, Schmidt M, et al. LM02-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science. 2003; 302:415–419.

    Article  Google Scholar 

  46. Hacein-Bey-Abina S, Garrigue A, Wang GP, et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest. 2008 Sept; 118(9):3132–3142.

    Article  Google Scholar 

  47. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006 Aug 25; 126(4):663–676.

    Article  Google Scholar 

  48. Carneiro FA, Bianconi ML, Weissmuller G, Stauffer F, Da Poian AT. Membrane recognition by vesicular stomatitis virus involves enthalpy-driven protein-lipid interactions. J Virol. 2002 Mar 19; 76(8):3756–3764.

    Article  Google Scholar 

  49. Clements MO, Godfrey A, Crossley J, Wilson SJ, Takeuchi Y, Boshoff C. Lentiviral manipulation of gene expression in human adult and embryonic stem cells. Tissue Eng. 2006 Jul; 12(7):1741–1751.

    Article  Google Scholar 

  50. Ma Y, Ramezani A, Lewis R, Hawley RG, Thomson JA. High-level sustained transgene expression in human embryonic stem cells using lentiviral vectors. Stem Cells. 2003; 21(1):111–117.

    Article  Google Scholar 

  51. Kobayashi N, Rivas-Carrillo JD, Soto-Gutierrez A, et al. Gene delivery to embryonic stem cells. Birth Defects Res C Embryo Today. 2005 Mar; 75(1):10–18.

    Article  Google Scholar 

  52. Menendez P, Wang L, Bhatia M. Genetic manipulation of human embryonic stem cells: a system to study early human development and potential therapeutic applications. Curr Gene Ther. 2005 Aug; 5(4):375–385.

    Article  Google Scholar 

  53. Suter DM, Cartier L, Bettiol E, et al. Rapid generation of stable transgenic embryonic stem cell lines using modular lentivectors. Stem Cells. 2006 Mar; 24(3):615–623.

    Article  Google Scholar 

  54. Ivey K, Muth A, Arnold J, et al. MircoRNA regulation of cell lineages in mouse and human embryonic stem cells. Cell Stem Cell. 2008; 2:219–229.

    Article  Google Scholar 

  55. Philpott N, Thrasher A. Use of nonintegrating lentiviral vectors for gene therapy. Hum Gene Ther. 2007 Jun; 18:483–489.

    Article  Google Scholar 

  56. Lombardo A, Genovese P, Beausejour CM, et al. Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery. Nat Biotechnol. 2007 Nov; 25(11):1298–1306.

    Article  Google Scholar 

  57. Aoi T, Yae K, Nakagawa M, et al. Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science. 2008 Aug 1; 321(5889):699–702.

    Article  Google Scholar 

  58. Kim JB, Sebastiano V, Wu G, et al. Oct4-induced pluripotency in adult neural stem cells. Cell. 2009 Feb 6; 136(3):411–419.

    Article  Google Scholar 

  59. Maherali N, Sridharan R, Xie W, et al. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell. 2007 Jun 7; 1(1):55–70.

    Article  Google Scholar 

  60. Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature. 2007 Jul 19; 448(7151):313–317.

    Article  Google Scholar 

  61. Wernig M, Meissner A, Foreman R, et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature. 2007 Jul 19; 448(7151):318–324.

    Article  Google Scholar 

  62. Huangfu D, Maehr R, Guo W, et al. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol. 2008 Jul; 26(7):795–797.

    Article  Google Scholar 

  63. Maherali N, Hochedlinger K. Guidelines and techniques for the generation of induced pluripotent stem cells. Cell Stem Cell. 2008 Dec 4; 3(6):595–605.

    Article  Google Scholar 

  64. Eminli S, Jaenisch R, Hochedlinger K. Strategies to induce nuclear reprogramming. Ernst Schering Found Symp Proc. 2006; 5:83–98.

    Google Scholar 

  65. Shi Y, Do JT, Desponts C, Hahm HS, Scholer HR, Ding S. A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell. 2008 Jun 5; 2(6):525–528.

    Article  Google Scholar 

  66. Jiang J, Chan YS, Loh YH, et al. A core Klf circuitry regulates self-renewal of embryonic stem cells. Nat Cell Biol. 2008 Mar; 10(3):353–60.

    Article  Google Scholar 

  67. Kim JB, Zaehres H, Wu G, et al. Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature. 2008 Jul 31; 454(7204):646–650.

    Article  Google Scholar 

  68. Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007; 131:1–12.

    Article  Google Scholar 

  69. Pesce M, Gross MK, Scholer HR. In line with our ancestors: Oct-4 and the mammalian germ. Bioessays. 1998 Sept; 20(9):722–732.

    Article  Google Scholar 

  70. Fong H, Hohenstein KA, Donovan PJ. Regulation of self-renewal and pluripotency by Sox2 in human embryonic stem cells. Stem Cells. 2008 Aug; 26(8):1931–1938.

    Article  Google Scholar 

  71. Boyer LA, Lee TI, Cole MF, et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 2005 Sept 23; 122(6):947–956.

    Article  Google Scholar 

  72. Wolf D, Goff SP. TRIM28 mediates primer binding site-targeted silencing of murine leukemia virus in embryonic cells. Cell. 2007 Oct 5; 131(1):46–57.

    Article  Google Scholar 

  73. Dimos JT, Rodolfa KT, Niakan KK, et al. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neutrons. Science. 2008 Aug 29; 321(5893):1218–21. Epub 2008 Jul 31.

    Google Scholar 

  74. Stadtfeld M, Maherali N, Breault DT, Hochedlinger K. Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell. 2008 Mar 6; 2(3):230–240.

    Article  Google Scholar 

  75. Lois C, Hong EJ, Pease S, Brown EJ, Baltimore D. Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors. Science. 2002 Feb 1; 295(5556):868–872.

    Article  Google Scholar 

  76. Brambrink T, Foreman R, Welstead GG, et al. Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells. Cell Stem Cell. 2008 Feb 7; 2(2):151–159.

    Article  Google Scholar 

  77. Hockemeyer D, Soldner F, Cook EG, Gao Q, Mitalipova M, Jaenisch R. A drug-inducible system for direct reprogramming of human somatic cells to pluripotency. Cell Stem Cell. 2008 Sept 11; 3(3):346–353.

    Article  Google Scholar 

  78. Maherali N, Ahfeldt T, Rigamonti A, Utikal J, Cowan C, Hochedlinger K. A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell. 2008 Sept 11; 3(3):340–345.

    Article  Google Scholar 

  79. Wernig M, Lengner CJ, Hanna J, et al. A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types. Nat Biotechnol. 2008 Aug; 26(8):916–924.

    Article  Google Scholar 

  80. Kustikova O, Fehse B, Modlich U, et al. Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking. Science. 2005 May 20; 308(5725):1171–1174.

    Article  Google Scholar 

  81. Nakagawa M, Koyanagi M, Tanabe K, et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol. 2008 Jan; 26(1):101–106.

    Article  Google Scholar 

  82. Narazaki G, Uosaki H, Teranishi M, et al. Directed and systematic differentiation of cardiovascular cells from mouse induced pluripotent stem cells. Circulation. 2008; 118:498–506.

    Article  Google Scholar 

  83. Meissner A, Wernig M, Jaenisch R. Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells. Nat Biotechnol. 2007 Oct; 25(10):1177–1181.

    Article  Google Scholar 

  84. Bosnali M, Edenhofer F. Generation of transducible versions of transcription factors Oct4 and Sox2. Biol Chem. 2008 July; 389(7):851–861.

    Article  Google Scholar 

  85. Yanez-Munoz RJ, Balaggan KS, MacNeil A, et al. Effective gene therapy with nonintegrating lentiviral vectors. Nat Med. 2006 Mar; 12(3):348–353.

    Article  Google Scholar 

  86. Okita K, Nakagawa M, Hyenjong H, Ichisaka T, Yamanaka S. Generation of mouse induced pluripotent stem cells without viral vectors. Science. 2008 Nov 7; 322(5903):949–953.

    Article  Google Scholar 

  87. Caspi O, Huber I, Kehat I, et al. Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. J Am Coll Cardiol. 2007 Nov 6; 50(19):1884–1893.

    Article  Google Scholar 

  88. Laflamme M, Chen K, Naumova A, et al. Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotech. 2007; 25:1015–1024.

    Article  Google Scholar 

  89. van Laake LW, Passier R, Doevendans PA, Mummery CL. Human embryonic stem cell-derived cardiomyocytes and cardiac repair in rodents. Circ Res. 2008 May 9; 102(9):1008–1010.

    Article  Google Scholar 

  90. Yang L, Soonpaa MH, Adler ED, et al. Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population. Nature. 2008 May 22; 453(7194):524–528.

    Article  Google Scholar 

  91. Mauritz C, Schwanke K, Reppel M, et al. Generation of functional murine cardiac myocytes from induced pluripotent stem cells. Circulation. 2008; 118:507–517.

    Article  Google Scholar 

  92. Zhang J, Wilson GF, Soerens AG, et al. Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ Res. 2009 Feb 27; 104(4):e30–41.

    Article  Google Scholar 

  93. Verlinsky Y, Strelchenko N, Kukharenko V, et al. Human embryonic stem cell lines with genetic disorders. Reprod Biomed Online. 2005 Jan; 10(1):105–110.

    Article  Google Scholar 

  94. Hanna J, Wernig M, Markoulaki S, et al. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science. 2007 Dec 21; 318(5858):1920–1923.

    Article  Google Scholar 

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Acknowledgments

The authors thank S. Mukherjee (Institute for Child Health, London) for help with Fig. 3.

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Kane, N.M., Denning, C., Baker, A.H. (2011). Genetic Modification of Human Embryonic and Induced Pluripotent Stem Cells: Viral and Non-viral Approaches. In: Artmann, G., Minger, S., Hescheler, J. (eds) Stem Cell Engineering. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-11865-4_7

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