Skip to main content
SpringerLink
Log in

Cell replacement therapy and the evasion of destructive immunity

  • Original Article
  • Published:
Stem Cell Reviews Aims and scope Submit manuscript

Abstract

The potential of human embryonic stem (ES) cells to meet the growing demand for cell types and tissues for the treatment of chronic and degenerative diseases has been widely acclaimed. Nevertheless, their use in cell replacement therapy poses a number of significant challenges, not least of which is their subsequent rejection by the recipient’s immune system. Here we explore the extent of the immunological barriers encountered and evaluate the potential of different approaches to overcoming these issues of which somatic nuclear transfer (SNT) and the induction of transplanation tolerance are currently the most promising.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Science 1998;282:1145–1147.

    Article  PubMed  CAS  Google Scholar 

  2. Li H, Roblin G, Liu H, Heller S. Proc Natl Acad Sci USA 2003;100:13,495–13,500.

    CAS  Google Scholar 

  3. Shirahashi H, Wu J, Yamamoto N, et al. Cell Transplant 2004;13:197–211.

    PubMed  Google Scholar 

  4. Assady S, Maor G, Amit M, Itskovitz-Eldor J, Skorecki KL, Tzukerman M. Diabetes 2001;50:1691–1697.

    Article  PubMed  CAS  Google Scholar 

  5. Reubinoff BE, Itsykson P, Turetsky T, et al. Nat Biotechnol 2001;19:1134–1140.

    Article  PubMed  CAS  Google Scholar 

  6. Zhang S-C, Wernig M, Duncan ID, Brustle O, Thomson JA. Nat Biotechnol 2001;19:1129–1133.

    Article  PubMed  CAS  Google Scholar 

  7. Zeng X, Cai J, Chen J, et al. Stem Cells 2004;22:925–940.

    Article  PubMed  CAS  Google Scholar 

  8. Lindvall O, Kokaia Z, Martinez-Serrano A. Nat Med 2004;10:S42-S50.

    Article  PubMed  CAS  Google Scholar 

  9. Langston JW. J Clin Invest 2005;115:23–25.

    Article  PubMed  CAS  Google Scholar 

  10. Kim JH, Auerbach JM, Rodriguez-Gomez JA, et al. Nature 2002;418:50–56.

    Article  PubMed  CAS  Google Scholar 

  11. Takagi Y, Takahashi J, Saiki H, et al. J Clin Invest 2005;115:102–109.

    Article  PubMed  CAS  Google Scholar 

  12. Kehat I, Khimovich L, Caspi O, et al. Nat Biotechnol 2004;22:1282–1289.

    Article  PubMed  CAS  Google Scholar 

  13. Strom TB, Field LJ, Ruediger M. Curr Opin Immunol 2002;14:601–605.

    Article  PubMed  CAS  Google Scholar 

  14. Fairchild PJ. J Peptide Sci 1998;4:182–194.

    Article  CAS  Google Scholar 

  15. Drukker M, Katz G, Urbach A, et al. Proc Natl Acad Sci USA 2002;99:9864–9869.

    Article  PubMed  CAS  Google Scholar 

  16. Li L, Baroja ML, Majumdar A, et al. Stem Cells 2004;22:448–456.

    Article  PubMed  CAS  Google Scholar 

  17. Banchereau J, Steinman RM. Nature 1998;392:245–252.

    Article  PubMed  CAS  Google Scholar 

  18. Lechler R, Ng WF, Steinman RM. Immunity 2001;14:357–368.

    Article  PubMed  CAS  Google Scholar 

  19. Goulmy E. Immunol Rev 1997;157:125–140.

    Article  PubMed  CAS  Google Scholar 

  20. Simpson E, Roopernian D. Curr Opin Immunol 1997;9:655–661.

    Article  PubMed  CAS  Google Scholar 

  21. Lanza RP, Cibelli JB, West MD. Nat Med 1999;5:975–977.

    Article  PubMed  CAS  Google Scholar 

  22. Mombaerts P. Proc Natl Acad Sci USA 2003;100:11,924–11,925.

    Article  CAS  Google Scholar 

  23. Lanza RP, Chung HY, Yoo JJ, et al. Nat Biotechnol 2002;20:689–696.

    Article  PubMed  CAS  Google Scholar 

  24. Auchincloss H, Bonventre JV. Nat Biotechnol 2002;20:665–666.

    Article  PubMed  CAS  Google Scholar 

  25. Bradley JA, Bolton EM, Pedersen PA. Nat Rev Immunol 2002;2:859–871.

    Article  PubMed  CAS  Google Scholar 

  26. Fairchild PJ, Cartland S, Nolan KF, Waldmann H. Trends Immunol 2004;25:465–470.

    Article  PubMed  CAS  Google Scholar 

  27. Klug MG, Soonpaa MH, Koh GY, Field LJ. J Clin Invest 1996;98:216–224.

    PubMed  CAS  Google Scholar 

  28. Li M, Pevny L, Lovell-Badge R, Smith A. Curr Biol 1998;8:971–974.

    Article  PubMed  CAS  Google Scholar 

  29. Lechler RI, Batchelor JR. J Exp Med 1982;155:31–41.

    Article  PubMed  CAS  Google Scholar 

  30. Waldmann H, Cobbold SP. Immunity 2001;14:399–406.

    Article  PubMed  CAS  Google Scholar 

  31. Wood KJ, Sakaguchi S. Nat Rev Immunol 2003;3:199–210.

    Article  PubMed  CAS  Google Scholar 

  32. Chen T-C, Cobbold SP, Fairchild PJ, Waldmann H. J Immunol 2004;172:5900–5907.

    PubMed  CAS  Google Scholar 

  33. Chen T-C, Waldmann H, Fairchild PJ. J Clin Invest 2004;113:1754–1762.

    Article  PubMed  CAS  Google Scholar 

  34. Jonuleit H, Schmitt E, Schuler G, Knop J, Enk EH. J Exp Med 2000;192:1213–1222.

    Article  PubMed  CAS  Google Scholar 

  35. Roncarolo M-G, Levings MK, Traversari C. J Exp Med 2001;193:F5-F9.

    Article  PubMed  CAS  Google Scholar 

  36. Zheng XX, Sanchez-Fueyo A, Sho M, Domenig C, Sayegh MH, Strom TB. Immunity 2003;19:503–514.

    Article  PubMed  CAS  Google Scholar 

  37. Lechler RI, Garden OA, Turka LA. Nat Rev Immunol 2003;3:147–158.

    Article  PubMed  CAS  Google Scholar 

  38. Eiges R, Schuldiner M, Drukker M, Yanuka O, Itskovitz-Eldor J, Benvenisty N. Curr Biol 2001;11:514–518.

    Article  PubMed  CAS  Google Scholar 

  39. Park S, Kim EY, Ghil GS, et al. Neurosci Lett 2003;353:91–94.

    Article  PubMed  CAS  Google Scholar 

  40. Matin MM, Walsh JR, Gokhale PJ, et al. Stem Cells 2004;22:659–668.

    Article  PubMed  CAS  Google Scholar 

  41. Zwaka TP, Thomson JA. Nat Biotechnol 2003;21:319–321.

    Article  PubMed  CAS  Google Scholar 

  42. Streilein JW. Nat Rev Immunol 2003;3:879–889.

    Article  PubMed  CAS  Google Scholar 

  43. Erlebacher A. Curr Opin Immunol 2001;13:590–593.

    Article  PubMed  CAS  Google Scholar 

  44. Mellor AL, Munn DH. Trends Immunol 1999;20:469–473.

    CAS  Google Scholar 

  45. Munn DH, Zhou M, Attwood JT, et al. Science 1998;281:1191–1193.

    Article  PubMed  CAS  Google Scholar 

  46. Schepers K, Schumacher TMN. Nat Med 2003;9:1253–1254.

    Article  PubMed  CAS  Google Scholar 

  47. Uyttenhove C, Pilotte L, Theate I, et al. Nat Med 2003;9:1269–1274.

    Article  PubMed  CAS  Google Scholar 

  48. Gabrilovich D. Nat Rev Immunol 2004;4:941–952.

    Article  PubMed  CAS  Google Scholar 

  49. Curiel TJ, Coukos G, Zou L, et al. Nat Med 2004;10:942–949.

    Article  PubMed  CAS  Google Scholar 

  50. Alexander AM, Crawford M, Bertera S, et al. Diabetes 2002;51:356–365.

    Article  PubMed  CAS  Google Scholar 

  51. Kaufman DS, Hanson ET, Lewis RL, Auerbach R, Thomson JA. Proc Natl Acad Sci USA 2001;98:10,716–10,721.

    Article  CAS  Google Scholar 

  52. Sykes M. Immunity 2001;14:417–424.

    Article  PubMed  CAS  Google Scholar 

  53. Burt RK, Verda L, Kim D-A, Oyama Y, Luo K, Link C. J Exp Med 2004;199:895–904.

    Article  PubMed  CAS  Google Scholar 

  54. Moustafa ME, Srivastava AS, Nedelcu E, et al. Transplantation 2004;78:1274–1284.

    Article  PubMed  Google Scholar 

  55. Fändrich F, Lin X, Chai GX, et al. Nat Med 2002;8:171–178.

    Article  PubMed  Google Scholar 

  56. Rathjen J, Rathjen PD. Curr Opin Genet Dev 2001;11:587–594.

    Article  PubMed  CAS  Google Scholar 

  57. Qin S, Cobbold SP, Pope H, et al. Science 1993;259:974–977.

    Article  PubMed  CAS  Google Scholar 

  58. Fairchild PJ, Waldmann H. Curr Opin Immunol 2000;12:528–535.

    Article  PubMed  CAS  Google Scholar 

  59. Hawiger D, Inaba K, Dorsett Y, et al. J Exp Med 2001;194:769–779.

    Article  PubMed  CAS  Google Scholar 

  60. Bonifaz L, Bonnyay D, Mahnke K, Rivera M, Nussenzweig MC, Steinman RM. J Exp Med 2002;196:1627–1638.

    Article  PubMed  CAS  Google Scholar 

  61. Mahnke K, Qian Y, Knop J, Enk AH. Blood 2003;101:4862–4869.

    Article  PubMed  CAS  Google Scholar 

  62. Dhodapkar MW, Steinman RM, Krasovsky J, Munz C, Bhardwaj N. J Exp Med 2001;193:233–238.

    Article  PubMed  CAS  Google Scholar 

  63. Fairchild PJ, Brook FA, Gardner RL, et al. Curr Biol 2000;10:1515–1518.

    Article  PubMed  CAS  Google Scholar 

  64. Fairchild PJ, Nolan KF, Waldmann H. Methods Enzymol 2003;365:169–186.

    Article  PubMed  Google Scholar 

  65. Fairchild PJ, Nolan KF, Graça L, Waldmann H. Transplantation 2003;76:606–608.

    Article  PubMed  Google Scholar 

  66. Fairchild PJ, Nolan KF, Cartland S, Waldmann H. Int Immunopharmacol 2004;5:13–21.

    Article  CAS  Google Scholar 

  67. De Smedt T, Van Mechelen M, De Becker G, Urbain J, Leo O, Moser M. Eur J Immunol 1997;27:1229–1235.

    Article  PubMed  Google Scholar 

  68. Penna G, Adorini L. J Immunol 2000;164:2405–2411.

    PubMed  CAS  Google Scholar 

  69. Gregori S, Castorati M, Amuchastegui S, Smiroldo S, Davalli AM, Adorini L. J Immunol 2001;167:1945–1953.

    PubMed  CAS  Google Scholar 

  70. Cheng P, Nefedova Y, Miele L, Osborne BA, Gabrilovich D. Blood 2003;102:3980–3988.

    Article  PubMed  CAS  Google Scholar 

  71. Quezada SA, Jarvinen LZ, Lind EF, Noelle RJ. Annu Rev Immunol 2004;22:307–328.

    Article  PubMed  CAS  Google Scholar 

  72. Hochweller K, Anderton SM. Eur J Immunol 2004;34:990–998.

    Article  PubMed  CAS  Google Scholar 

  73. Martin E, O’Sullivan B, Low P, Thomas R. Immunity 2003;18:155–167.

    Article  PubMed  CAS  Google Scholar 

  74. Fujii S, Liu K, Smith C, Bonito AJ, Steinman RM. J Exp Med 2004;199:1607–1618.

    Article  PubMed  CAS  Google Scholar 

  75. Tone M, Tone Y, Fairchild PJ, Wykes M, Waldmann H. Proc Natl Acad Sci USA 2001;98:1751–1756.

    Article  PubMed  CAS  Google Scholar 

  76. Ferguson TA, Herndon J, Elzey B, Griffith TS, Schoenberger S, Green DR. J Immunol 2002;168:5589–5595.

    PubMed  CAS  Google Scholar 

  77. Liu K, Iyoda T, Saternus M, Kimura Y, Inaba K, Steinman RM. J Exp Med 2002;196:1091–1097.

    Article  PubMed  CAS  Google Scholar 

  78. Quezada SA, Fuller B, Jarvinen LZ, et al. Blood 2003;102:1920–1926.

    Article  PubMed  CAS  Google Scholar 

  79. Mirenda V, Berton I, Read J, et al. J Am Soc Nephrol 2004;15:987–997.

    Article  PubMed  CAS  Google Scholar 

  80. Zhan X, Dravid G, Ye Z, et al. Lancet 2004;364:163–171.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sir William Dunn School of Pathology, University of Oxford, South Parks Road, OX1 3RE, Oxford, UK

    Paul J. Fairchild, Nathan J. Robertson, Siân Cartland, Kathleen F. Nolan & Herman Waldmann

Authors
  1. Paul J. Fairchild
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nathan J. Robertson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Siân Cartland
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kathleen F. Nolan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Herman Waldmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul J. Fairchild.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fairchild, P.J., Robertson, N.J., Cartland, S. et al. Cell replacement therapy and the evasion of destructive immunity. Stem Cell Rev 1, 159–167 (2005). https://doi.org/10.1385/SCR:1:2:159

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/SCR:1:2:159

Keywords

Search

Navigation