Stem Cell Reviews

, Volume 2, Issue 4, pp 331–340 | Cite as

Cell fusion for reprogramming pluripotency

Toward elmination of the pluripotent genome
  • Danièle Pralong
  • Alan O. Trounson
  • Paul J. Verma


Embryonic stem cell (ESC) technology should enable the generation of specific cell types for the study and treatment of human diseases. Therapeutic cloning provides a way to generate ESCs genetically matched to diseased individuals through nuclear reprogramming of the somatic genome. However, practical and ethical limitations associated with therapeutic cloning are calling for the development of oocyte- and-embryo-free alternatives for obtaining of autologous pluripotent cells for transplantation therapy. An alternative approach to reprogram the somatic genome involves fusion between somatic and pluripotent cells. Potential fusion partners with reprogrmaming activities include embryonal carcinoma cells, embryonic germ cells, and ESCs.

Experimental evidence is now available, which demonstrates that mouse and human somatic cells can be reprogrammed by fusion to form pluripotent hybrid cells. Recent progress infusion-based reprogramming is reviewed with reference to the developmenta potency of hybrid cells as well as genetic and epigenetic correlates of reprogramming. However, hybrid cells lack therapeutic potential because of their abnormal ploidy and the presence of nonautologous genes from the pluripotent parent. We discuss the potential of fusion-based reprogramming for the generation of diploid, autologous pluripotent cells using two alternative routes: the enucleation of ESCs and the fusion of such cytoplasts to somatic cell karyplasts or intact somatic cells, and the selective elimination of the pluripotent genome following fusion to the somatic partner. Finally, these approaches are discussed in the light of recent progress showing that overexpression of embryonic transcription factors can restore a state of pluripotency to somatic cells.

Index Entries

Reprogramming cell fusion pluripotent embryonic stem cells nuclear transfer therapeutic cloning 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH. Nature 1997;385:810–813.PubMedCrossRefGoogle Scholar
  2. 2.
    Wakayama T, Perry AC, Zuccotti M, Johnson KR, Yanagimachi R. Nature 1998;394:369–374.PubMedCrossRefGoogle Scholar
  3. 3.
    Meissner A, Jaenisch R. Dev Dyn 2006;235:2460–2469.PubMedCrossRefGoogle Scholar
  4. 4.
    Kawase E, Yamazaki Y, Yagi T, Yanagimachi R, Pedersen RA. Genesis 2000;28:156–163.PubMedCrossRefGoogle Scholar
  5. 5.
    Munsie MJ, Michalska AE, O'Brien CM, Trounson AO, Pera MF, Mountford PS. Curr Biol 2000;10:989–992.PubMedCrossRefGoogle Scholar
  6. 6.
    Wakayama T, Tabar V, Rodriguez I, Perry AC, Studer L, Mombaerts P. Science 2001;292:740–743.PubMedCrossRefGoogle Scholar
  7. 7.
    Hochedlinger K, Jaenisch R. Nature 2002;415:1035–1038.PubMedCrossRefGoogle Scholar
  8. 8.
    Eggan K, Baldwin K, Tackett M, et al. Nature 2004;428:44–49.PubMedCrossRefGoogle Scholar
  9. 9.
    Inoue K, Wakao H, Ogonuki N, et al. Curr Biol 2005;15:1114–1118.PubMedCrossRefGoogle Scholar
  10. 10.
    Wakayama S, Mizutani E, Kishigami S, et al. J Reprod Dev 2005;51:765–772.PubMedCrossRefGoogle Scholar
  11. 11.
    Hochedlinger K, Jaenisch R. Nature 2006;441:1061–1067.PubMedCrossRefGoogle Scholar
  12. 12.
    Dean W, Santos F, Reik W. Semin Cell Dev Biol 2003;14:93–100.PubMedCrossRefGoogle Scholar
  13. 13.
    Boiani M, Eckardt S, Scholer HR, McLaughlin KJ. Gene Dev 2002;16:1209–1219.PubMedCrossRefGoogle Scholar
  14. 14.
    Bortvin A, Eggan K, Skaletsky H, et al. Development 2003; 130:1673–1680.PubMedCrossRefGoogle Scholar
  15. 15.
    Rideout WM 3rd, Eggan K, Jaenisch R. Science 2001;293: 1093–1098.PubMedCrossRefGoogle Scholar
  16. 16.
    Hochedlinger K, Jaenisch R. Curr Opin Cell Biol 2002;14:741–748.PubMedCrossRefGoogle Scholar
  17. 17.
    Blelloch R, Wang Z, Meissner A, Pollard S, Smith A, Jaenisch R. Stem Cells 2006;Epub ahead of print.Google Scholar
  18. 18.
    Kishigami S, Mizutani E, Ohta H, et al. Biochem Biophys Res Commun 2006;340:183–189.PubMedGoogle Scholar
  19. 19.
    Dennis C. Nature 2006;439:652–655.PubMedCrossRefGoogle Scholar
  20. 20.
    Taranger CK, Noer A, Sorensen AL, Hakelien AM, Boquest AC, Collas P. Mol Biol Cell 2005;16:5719–5735.PubMedCrossRefGoogle Scholar
  21. 21.
    Meissner A, Jaenisch R. Nature 2006;439:212–215.PubMedCrossRefGoogle Scholar
  22. 22.
    Klimanskaya I, Chung Y, Becker S, Lu SJ, Lanza R. Nature 2006; 444:481–485.PubMedCrossRefGoogle Scholar
  23. 23.
    Hubner K, Fuhrmann G, Christenson LK, et al. Science 2003;300:1251–1256.PubMedCrossRefGoogle Scholar
  24. 24.
    Baron MH, Maniatis T. Cell 1986;46:591–602.PubMedCrossRefGoogle Scholar
  25. 25.
    Blau HM, Blakely BT. Semin Cell Dev Biol 1999;10:267–272.PubMedCrossRefGoogle Scholar
  26. 26.
    Miller RA, Ruddle FH. Cell 1976;9:45–55.PubMedCrossRefGoogle Scholar
  27. 27.
    Miller RA, Ruddle FH. Dev Biol 1977;56:157–173.PubMedCrossRefGoogle Scholar
  28. 28.
    Miller RA, Ruddle FH. Somatic Cell Genet 1977;3:247–261.PubMedCrossRefGoogle Scholar
  29. 29.
    Andrews PW, Goodfellow PN. Somatic Cell Genet 1980;6:271–284.PubMedCrossRefGoogle Scholar
  30. 30.
    Forejt J, Gregorova S, Dohnal K, Nosek J. Cell Differ 1984; 15:229–234.PubMedCrossRefGoogle Scholar
  31. 31.
    Flasza M, Shering AF, Smith K, Andrews PW, Talley P, Johnson PA. Cloning Stem Cells 2003;5:339–354.PubMedCrossRefGoogle Scholar
  32. 32.
    Hajkova P, Erhardt S, Lane N, et al. Mech Dev 2002;117:15–23.PubMedCrossRefGoogle Scholar
  33. 33.
    Tada M, Tada T, Lefebvre L, Barton SC, Surani MA. EMBO J 1997;16:6510–6520.PubMedCrossRefGoogle Scholar
  34. 34.
    Rathjen J, Haines BP, Hudson KM, Nesci A, Dunn S, Rathjen PD. Development 2002;129:2649–2661.PubMedGoogle Scholar
  35. 35.
    Matveeva NM, Shilov AG, Kaftanovskaya EM et al. Mol Reprod Dev 1998;50:128–138.PubMedCrossRefGoogle Scholar
  36. 36.
    Tada M, Takahama Y, Abe K, Nakatsuji N, Tada T. Curr Biol 2001;11:1553–1558.PubMedCrossRefGoogle Scholar
  37. 37.
    Ying Q, Nichols J, Evans EP, Smith AG. Nature 2002;416:545–548.PubMedCrossRefGoogle Scholar
  38. 38.
    Pells S, Di Domenico AI, Gallagher EJ, McWhir J. Cloning Stem Cells 2002;4:331–338.PubMedCrossRefGoogle Scholar
  39. 39.
    Terada N, Hamazaki T, Oka M, et al. Nature 2002;416:542–545.PubMedCrossRefGoogle Scholar
  40. 40.
    Weimann JM, Johnsson CB, Trejo A, Blau HM. Nat Cell Biol 2003;5:959–966.PubMedCrossRefGoogle Scholar
  41. 41.
    Tada M, Morizane A, Kimura H, et al. Dev Dyn 2003;227:504–510.PubMedCrossRefGoogle Scholar
  42. 42.
    Hatano SY, Tada M, Kimura H, et al. Mech Dev 2005;122:67–79.PubMedCrossRefGoogle Scholar
  43. 43.
    Fry CJ, Peterson CL. Curr Biol 2001;11:R185-R197.PubMedCrossRefGoogle Scholar
  44. 44.
    Lachner M, O'Sullivan RJ, Jenuwein T. J Cell Sci 2003; 116:2117–2124.PubMedCrossRefGoogle Scholar
  45. 45.
    Kimura H, Tada M, Nakatsuji N, Tada T. Mol Cell Biol 2004; 24:5710–5720.PubMedCrossRefGoogle Scholar
  46. 46.
    Cowan CA, Atienza J, Melton DA, Eggan K. Science 2005; 309:1369–1373.PubMedCrossRefGoogle Scholar
  47. 47.
    Yu J, Vodyanik MA, He P, Slukvin II, Thomson JA. Stem Cells 2006;4:168–176.CrossRefGoogle Scholar
  48. 48.
    Vassilopoulos G, Russell DW. Curr Opin Genet Dev 2003;13:480–485.PubMedCrossRefGoogle Scholar
  49. 49.
    Matveeva NM, Pristyazhnyuk IE, Temirova SA, et al. Mol Reprod Dev 2005;71:305–314.PubMedCrossRefGoogle Scholar
  50. 50.
    Bunn CL, Eisenstadt JM. Somatic Cell Genet 1977;3:335–341.PubMedCrossRefGoogle Scholar
  51. 51.
    Hakelien AM, Landsverk HB, Robl JM, Skalhegg BS, Collas P. Nat Biotechnol 2002;20:460–466.PubMedCrossRefGoogle Scholar
  52. 52.
    Byrne JA, Simonsson S, Western PS, Gurdon JB. Curr Biol 2003;13:1206–1213.PubMedCrossRefGoogle Scholar
  53. 53.
    Do JT, Scholer HR. Stem Cells 2004;22:941–949.PubMedCrossRefGoogle Scholar
  54. 54.
    Strelchenko N, Kukharenko V, Shkumatov A, Verlinsky O, Kuliev A, Verlinsky Y. Reprod Biomed Online 2006;12:107–111.PubMedCrossRefGoogle Scholar
  55. 55.
    Pralong D, Mrozik K, Occhiodoro F, et al. Cloning Stem Cells 2005;7:265–271.PubMedGoogle Scholar
  56. 56.
    Pralong D, Lim ML, Vassiliev I, et al. Cloning Stem Cells 2005;7:272–278.PubMedCrossRefGoogle Scholar
  57. 57.
    Blau HM, Baltimore D. J Cell Biol 1991;12:781–783.CrossRefGoogle Scholar
  58. 58.
    McBurney MW. Cell 1977;12:653–662.PubMedCrossRefGoogle Scholar
  59. 59.
    Do JT, Scholer HR. Reprod Fertil Dev 2005;17:143–149.PubMedCrossRefGoogle Scholar
  60. 60.
    Silva J, Chambers I, Pollard S, Smith A. Nature 2006;441: 997–1001.PubMedCrossRefGoogle Scholar
  61. 61.
    Takahashi K, Yamanaka S. Cell 2006;126:663–676.PubMedCrossRefGoogle Scholar
  62. 62.
    Campbell KH, Loi P, Otaegui PJ, Wilmut I. Rev Reprod 1996;40–46.Google Scholar
  63. 63.
    Stead E, White J, Faast R, et al. Oncogene 2002;21:8320–8333.PubMedCrossRefGoogle Scholar
  64. 64.
    Latham KE. Differentiation 2004;72:11–22.PubMedCrossRefGoogle Scholar
  65. 65.
    Radomska HS, Eckhardt LA. J Immunol Methods 1995;188:209–217.PubMedCrossRefGoogle Scholar
  66. 66.
    Yeom YI, Fuhrmann G, Ovitt CE, et al. Development 1996; 122:881–894.PubMedGoogle Scholar
  67. 67.
    Matsumura H, Tada M, Otsuji T, et al. Nat. Methods 2007;4: 23–25.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2006

Authors and Affiliations

  • Danièle Pralong
    • 1
  • Alan O. Trounson
    • 2
  • Paul J. Verma
    • 1
  1. 1.Centre for Reproduction and Development, Monash Institute of Medical Research, MonashMonash UniversityClaytonAustralia
  2. 2.Monash Immunology and Stem Cell LaboratoriesMonash UniversityClaytonAustralia

Personalised recommendations