Stem Cell Reviews

, Volume 2, Issue 4, pp 341–349 | Cite as

The potential of cell fusion for human therapy



As donor organs and tissues for transplantation medicine are scarce, alternative methods for replacing damaged cells or restoring organ function are highly needed. Here, we consider the therapeutic potential of cell fusion. After highlighting the various contexts in which cells are known to fuse during mammalian development, we discuss the implications of the observation that cell fusion can occur with restorative effects following tissue damage or cell transplantation. There are still, however, many challenges facing those who wish to implement cell fusion as a therapeutic tool. These include identifying the best cells to use for reparative fusion, determining the best route of introducing these cells into the desired tissue, discovering methods to increase the incidence of cell fusion, and ensuring the functionality of the resulting fusion products. If these difficulties can be overcome, cell fusion might have therapeutic potential as highlighted by several recent transplantation studies.

Index entries

Differentiation epigenetic fusion heterokaryon hybrid nuclear transfer phenotypic dominance reprogramming stem cell synkaryon tetraploid therapy trans-differentiation transplant 


  1. 1.
    Schleiden M. Beitrage zur Phytogenesis 1838. pp. 137–176.Google Scholar
  2. 2.
    Schwann T. In Mikroskopische Untersuchungen uber die Ubereinstimmung in der Struckur und dem Wachsten der Thiere und Pflanzen Saunderschen Buchhandlung, Berlin, 1839.Google Scholar
  3. 3.
    Schwann T. In Microscopical researches into the accordance in the structure and growth of animals and plants. Sydenham Soc, London, 1847.Google Scholar
  4. 4.
    Chen EH, Olson EN: Science 2005;308:369–373.PubMedCrossRefGoogle Scholar
  5. 5.
    Wassarman PM, Jovine L, Qi H, Williams Z, Darie C, Litscher ES. Mol Cell Endocrinol 2005;234:95–103.PubMedCrossRefGoogle Scholar
  6. 6.
    Malassine A, Cronier L. Endocrine 2002;19:3–11.PubMedCrossRefGoogle Scholar
  7. 7.
    Benirschke K, Kaufmann P. In Pathology of the Human Placenta. Springer, New York, 2000.Google Scholar
  8. 8.
    Lieber RL. In: Skeletal Muscle Structure and Function. Lipincott Williams & Wilkins, Baltimore, 1992.Google Scholar
  9. 9.
    Wang X, Willenbring H, Akkari Y, et al. Nature 2003;422:897–901.PubMedCrossRefGoogle Scholar
  10. 10.
    Johnson SJ, Mathew J, MacSween RN, Bennett MK, Burt AD. J Clin Pathol 1994;47:1022–1027.PubMedCrossRefGoogle Scholar
  11. 11.
    Anderson JM. Curr Opin Hematol 2000;7:40–47.PubMedCrossRefGoogle Scholar
  12. 12.
    Kontani K, Rothman JH. Curr Biol 2005;15:R252-R254.PubMedCrossRefGoogle Scholar
  13. 13.
    Abmayr SM, Balagopalan L, Galletta BJ, Hong SJ. Int Rev Cytol 2003;225:33–89.PubMedGoogle Scholar
  14. 14.
    Duelli D, Lazebnik Y. Cancer Cell 2003;3;445–448.PubMedCrossRefGoogle Scholar
  15. 15.
    Ogle BM, Cascalho M, Platt JL. Nat Rev Mol Cell Biol 2005; 6:567–575.PubMedCrossRefGoogle Scholar
  16. 16.
    Chen MS, Tung KS, Coonrod SA, et al. Proc Natl Acad Sci USA 1996;96:11,830–11,835.Google Scholar
  17. 17.
    Kaji K, Oda S, Shikano T, et al. Nat Genet 2000;24:279–282.PubMedCrossRefGoogle Scholar
  18. 18.
    Yagi M, Miyamoto T, Sawatani Y, et al. J Exp Med 2005;202: 345–351.PubMedCrossRefGoogle Scholar
  19. 19.
    Horsley V, Pavlath GK. Cells Tissues Organs 2004;176:67–78.PubMedCrossRefGoogle Scholar
  20. 20.
    Wakelam MJ. Biochem J 1985;228:1–12.PubMedGoogle Scholar
  21. 21.
    Ohno-Shosaku T, Okada Y. Biochem Biophys Res Commun 1984;120:138–143.PubMedCrossRefGoogle Scholar
  22. 22.
    Ohno-Shosaku T, Hama-Inaba H, Okada Y. Cell Struct Funct 1984;9:193–196.PubMedCrossRefGoogle Scholar
  23. 23.
    Sullivan S, Waterfall M, Gallagher EJ, McWhir J, Pells S. Methods Mol Biol 2006;325:81–97.PubMedGoogle Scholar
  24. 24.
    Giraudo CG, Hu C, You D, et al. J Cell Biol 2005;170:249–260.PubMedCrossRefGoogle Scholar
  25. 25.
    Rash JE, Fambrough D. Dev Biol 1973;30:166–186.PubMedCrossRefGoogle Scholar
  26. 26.
    Przybylski RJ, Blumberg JM. Lab Invest 1966;15:836–863.PubMedGoogle Scholar
  27. 27.
    Lipton BH, Konigsberg IR. J Cell Biol 1972;53:348–364.PubMedCrossRefGoogle Scholar
  28. 28.
    Knudsen KA. In Membrane fusion In: Hoekstra D. (ed), Dekker, New York, 1992; pp. 601–626.Google Scholar
  29. 29.
    Morrison SJ. Curr Biol 2001;11:R7-R9.PubMedCrossRefGoogle Scholar
  30. 30.
    Hu E, Tontonoz P, Spiegelman BM. Proc Natl Acad Sci USA 1995; 92:9856–9860.PubMedCrossRefGoogle Scholar
  31. 31.
    Shen CN, Slack JM, Tosh D. Nat Cell Biol 2000;2:879–887.PubMedCrossRefGoogle Scholar
  32. 32.
    Funderburgh JL, Funderburgh ML, Mann MM, Corpuz L, Roth MR. J Biol Chem 2001;276:44,173–44,178.CrossRefGoogle Scholar
  33. 33.
    Condorelli G, Borello U, De Angelis L, et al. Proc Natl Acad Sci USA 2001;98:10,733–10,738.Google Scholar
  34. 34.
    Ying QL, Nichols J, Evans EP, Smith AG. Nature 2002;416:545–548.PubMedCrossRefGoogle Scholar
  35. 35.
    Terada N, Hamazaki T, Oka M, et al. Nature 2002;416:542–545.PubMedCrossRefGoogle Scholar
  36. 36.
    Pells S, Di Domenico AI, Gallagher EJ, McWhir J. Cloning Stem Cells 2002;4:331–338.PubMedCrossRefGoogle Scholar
  37. 37.
    Gibson AJ, Karasinski J, Relvas S, et al. J Cell Sci 1995;108(Pt 1) 207–214.PubMedGoogle Scholar
  38. 38.
    Relvas JB, Relvas HA, Relvas KE, Relvas W, Relvas DJ, Relvas WDJW. Basic App, Myol 1997;7:211–219.Google Scholar
  39. 39.
    Gussoni E, Soneoka Y, Strickland CD, et al. Nature 1999;401390–394.PubMedGoogle Scholar
  40. 40.
    Bittner RE, Schofer C, Weipoltshammer K, et al. Anat Embryol (Berl) 1999;199:391–396.CrossRefGoogle Scholar
  41. 41.
    Palermo AT, Labarge MA, Doyonnas R, Pomerantz J, Blau HM. Dev Biol 2005;279:336–344PubMedCrossRefGoogle Scholar
  42. 42.
    Camargo FD, Chambers SM, Goodell MA. Cell Prolif 2004; 37:55–65.PubMedCrossRefGoogle Scholar
  43. 43.
    O'Malley K, Scott EW. Exp Hematol 2004;32:131–134.PubMedCrossRefGoogle Scholar
  44. 44.
    Weimann JM, Charlton CA, Brazelton TR, Hackman RC, Blau HM. Proc Natl Acad Sci USA 2003;100:2088–2093.PubMedCrossRefGoogle Scholar
  45. 45.
    Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM, et al. Nature 2003;425:968–973.PubMedCrossRefGoogle Scholar
  46. 46.
    Vassilopoulos G, Wang PR, Russell DW. Nature 2003;422:901–904.PubMedCrossRefGoogle Scholar
  47. 47.
    Gridelli B, Remuzzi G. N Engl J Med 2003;343:404–410.CrossRefGoogle Scholar
  48. 48.
    Kohler G, Milstein C. Nature 1975;256:495–497.PubMedCrossRefGoogle Scholar
  49. 49.
    Trefzer U, Herberth G, Wohlan K, et al. Int J Cancer 2004;110: 730–740.PubMedCrossRefGoogle Scholar
  50. 50.
    Partridge TA. Gene Ther 2002;9:752–753.PubMedCrossRefGoogle Scholar
  51. 51.
    Willenbring H. Br J Surg 2005;92:923–924.PubMedCrossRefGoogle Scholar
  52. 52.
    Ferrari G, Cusella-DeAngelis G, Colletta M, et al. Science 1998;279:1528–1530.PubMedCrossRefGoogle Scholar
  53. 53.
    Quaini F, Urbanek K, Beltrami AP, et al. N Engl J Med 2002; 346:5–15.PubMedCrossRefGoogle Scholar
  54. 54.
    Deb A, Wang S, Skelding KA, et al. Circulation 2003:107: 1247–1249.PubMedCrossRefGoogle Scholar
  55. 55.
    Wagers AJ, Sherwood RI, Christensen JL, Weissman IL. Science 2002;297:2256–2259.PubMedCrossRefGoogle Scholar
  56. 56.
    Camargo FD, Green R, Capetanaki Y, Jackson KA, Goodell MA. Nat Med 2003;9:1520–1527.PubMedCrossRefGoogle Scholar
  57. 57.
    Doyonnas R, LaBarge MA, Sacco A, Charlton C, Blau HM. Proc Natl Acad Sci USA 2004;101:13,507–13,512.CrossRefGoogle Scholar
  58. 58.
    Willenbring H, Bailey AS, Foster M, et al. NatMed 2004;10:744–748.Google Scholar
  59. 59.
    Willenbring H, Grompe M. J Assist Reprod Genet 2003;20: 393–394.PubMedCrossRefGoogle Scholar
  60. 60.
    Boshart M, Nitsch D, Schutz G. Trends Genet 1993;9:240–245.PubMedCrossRefGoogle Scholar
  61. 61.
    Matveeva NM, Shilov AG, Kaftanovskaya, EM, et al. Mol Reprod Dev 1998;50:128–138.PubMedCrossRefGoogle Scholar
  62. 62.
    Tada M, Takahama Y, Abe K, Nakatsuji N, Tada T. Curr Biol 2001;11:1553–1558.PubMedCrossRefGoogle Scholar
  63. 63.
    Kimura H, Tada M, Nakatsuji N, Tada T. Mol Cell Biol 2004; 24:5710–5720.PubMedCrossRefGoogle Scholar
  64. 64.
    Tada M, Morizane A, Kimura H, et al. Dev Dyn 2003;227:504–510.PubMedCrossRefGoogle Scholar
  65. 65.
    Do JT, Scholer HR. Stem Cells 2004;22:941–949.PubMedCrossRefGoogle Scholar
  66. 66.
    Tada M, Tada T, Lefebvre L, Barton SC, Surani MA. EMBO J 1997; 16:6510–6520.PubMedCrossRefGoogle Scholar
  67. 67.
    Flasza M, Shering AF, Smith K, et al. Cloning Stem Cells 2003;5:339–354.PubMedCrossRefGoogle Scholar
  68. 68.
    Cowan CA, Atienza J, Melton DA, Eggan K. Science 2005; 309:1369–1373.PubMedCrossRefGoogle Scholar
  69. 69.
    Sullivan S, Pells S, Gallagher EJ, Hooper M, McWhir J. Cloning Stem Cells 2006;8:175–189.CrossRefGoogle Scholar
  70. 70.
    Takagi N, Yoshida MA, Sugawara O, Sasaki M. Cell 1983;34:1053–1062.PubMedCrossRefGoogle Scholar
  71. 71.
    Andrews PW, Goodfellow PN. Somatic Cell Genet 1980;6(2): 271–284.PubMedCrossRefGoogle Scholar
  72. 72.
    Khosla S, Dean W, Reik W, Feil R. Hum Reprod Update 2001; 7:419–427.PubMedCrossRefGoogle Scholar
  73. 73.
    Yao S, Chen S, Clark J, et al. Proc Natl Acad Sci USA 2006;103: 6907–6912.PubMedCrossRefGoogle Scholar
  74. 74.
    Liu Y, Song Z, Zhao Y, et al. Biochem Biophys Res Commun 2006.Google Scholar
  75. 75.
    Phimister EG. N Engl J Med 2005;353:1646–1647.PubMedCrossRefGoogle Scholar
  76. 76.
    Scarbrough PR, Hersh J, Kukolich MK, et al. Am J Med Genet 1984;19:29–37.PubMedCrossRefGoogle Scholar
  77. 77.
    Nakamura Y, Takaira M, Sato E, et al. Arch Pathol Lab Med 2003;127:1612–1614.PubMedGoogle Scholar
  78. 78.
    Golbus MS, Bachman R, Wiltse S, Hall BD. J Med Genet 1976; 13:329–332.PubMedCrossRefGoogle Scholar
  79. 79.
    Shiono H, Azumi J, Fujiwara M, Yamazaki H, Kikuchi K. Am J Med Genet 1988;29:543–547.PubMedCrossRefGoogle Scholar
  80. 80.
    Rizvi AZ, Swain JR, Davies PS, et al. Proc Natl Acad Sci USA 2006;103:6321–6325.PubMedCrossRefGoogle Scholar
  81. 81.
    Strelchenko N, Kukharenko V, Shkumatov A, et al. Reprod Biomed Online 2006;12:107–111.PubMedCrossRefGoogle Scholar
  82. 82.
    Fournier D, Estoup A, Orivel J, et al. Nature 2005;435:1230–1234.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2006

Authors and Affiliations

  1. 1.Stowers Medical Institute, Harvard Stem Cell InstituteHarvard UniversityCambridgeUSA
  2. 2.Department of Molecular and Cellular BiologyHarvard UniversityCambridgeUSA

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