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The Immunogenicity of Embryonic Stem Cells and Their Differentiated Progeny

Chapter
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)

Abstract

Embryonic stem (ES) cells are an attractive source for tissue regeneration and repair therapies. This is because in contrast to adult stem cells, ES cells possess unlimited self-renewal and pluripotent capacity. However, for the therapeutic application of ES cells to succeed, the transplanted ES cells must engraft successfully and survive long enough to exert a therapeutic effect. An important obstacle facing the in vivo engraftment and function of ES cells is the immunogenic barrier. In this chapter, we will begin by briefly discussing the safety concerns regarding the transplantation of ES cells and the factors that influence the behavior or misbehavior of transplanted ES cells. We will then discuss the in vitro immunogenic properties of ES cells, including the expression of major histocompatibility (MHC) antigens and minor histocompatibility (mH) antigens and how these properties evolve as undifferentiated cells mature towards more differentiated derivatives. We will also highlight the various (and in some instances conflicting) conclusions regarding the immunogenic properties of ES cells which have been drawn from prior in vitro studies and will conclude with a more extensive discussion of the immunogenic properties of ES cells when transplanted across allogeneic as well as xenogeneic immune barriers.

Keywords

Major Histocompatibility Complex Embryonic Stem Cell Major Histocompatibility Complex Class Teratoma Formation Major Histocompatibility Complex Antigen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by NIH R01 AI085575.

References

  1. 1.
    Zhang SC, Wernig M, Duncan ID, Brustle O, Thomson JA (2001) In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat Biotechnol 19:1129–1133PubMedCrossRefGoogle Scholar
  2. 2.
    Kim JH et al (2002) Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature 418:50–56PubMedCrossRefGoogle Scholar
  3. 3.
    McDonald JW et al (1999) Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nat Med 5:1410–1412PubMedCrossRefGoogle Scholar
  4. 4.
    Cao F et al (2008) Transcriptional and functional profiling of human embryonic stem cell-derived cardiomyocytes. PLoS ONE 3:e3474PubMedCrossRefGoogle Scholar
  5. 5.
    Chinzei R et al (2002) Embryoid-body cells derived from a mouse embryonic stem cell line show differentiation into functional hepatocytes. Hepatology 36:22–29PubMedCrossRefGoogle Scholar
  6. 6.
    Chadwick K et al (2003) Cytokines and BMP-4 promote hematopoietic differentiation of human embryonic stem cells. Blood 102:906–915PubMedCrossRefGoogle Scholar
  7. 7.
    Soria B et al (2000) Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes 49:157–162PubMedCrossRefGoogle Scholar
  8. 8.
    Bradley JA, Bolton EM, Pedersen RA (2002) Stem cell medicine encounters the immune system. Nat Rev Immunol 2:859–871PubMedCrossRefGoogle Scholar
  9. 9.
    Damjanov I, Solter D (1974) Experimental teratoma. Curr Top Pathol 59:69–130PubMedCrossRefGoogle Scholar
  10. 10.
    Ulbright TM (2005) Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues. Mod Pathol 18(Suppl 2):S61–S79PubMedCrossRefGoogle Scholar
  11. 11.
    Li JY, Christophersen NS, Hall V, Soulet D, Brundin P (2008) Critical issues of clinical human embryonic stem cell therapy for brain repair. Trends Neurosci 31:146–153PubMedCrossRefGoogle Scholar
  12. 12.
    Swijnenburg RJ et al (2008) In vivo imaging of embryonic stem cells reveals patterns of survival and immune rejection following transplantation. Stem Cells Dev 17:1023–1029PubMedCrossRefGoogle Scholar
  13. 13.
    Lee AS et al (2009) Effects of cell number on teratoma formation by human embryonic stem cells. Cell Cycle 8:2608–2612PubMedCrossRefGoogle Scholar
  14. 14.
    Cooke MJ, Stojkovic M, Przyborski SA (2006) Growth of teratomas derived from human pluripotent stem cells is influenced by the graft site. Stem Cells Dev 15:254–259PubMedCrossRefGoogle Scholar
  15. 15.
    Janeway CA, Mamula MJ, Rudensky A (1993) Rules for peptide presentation by MHC class II molecules. Int Rev Immunol 10:301–311PubMedCrossRefGoogle Scholar
  16. 16.
    Drukker M et al (2002) Characterization of the expression of MHC proteins in human embryonic stem cells. Proc Natl Acad Sci U S A 99:9864–9869PubMedCrossRefGoogle Scholar
  17. 17.
    Li L et al (2004) Human embryonic stem cells possess immune-privileged properties. Stem Cells 22:448–456PubMedCrossRefGoogle Scholar
  18. 18.
    Green DR, Ferguson TA (2001) The role of Fas ligand in immune privilege. Nat Rev Mol Cell Biol 2:917–924PubMedCrossRefGoogle Scholar
  19. 19.
    Grinnemo KH, Sylven C, Hovatta O, Dellgren G, Corbascio M (2008) Immunogenicity of human embryonic stem cells. Cell Tissue Res 331:67–78PubMedCrossRefGoogle Scholar
  20. 20.
    Grinnemo KH et al (2006) Human embryonic stem cells are immunogenic in allogeneic and xenogeneic settings. Reprod Biomed Online 13:712–724PubMedCrossRefGoogle Scholar
  21. 21.
    Drukker M et al (2006) Human embryonic stem cells and their differentiated derivatives are less susceptible to immune rejection than adult cells. Stem Cells 24:221–229PubMedCrossRefGoogle Scholar
  22. 22.
    Kofidis T et al (2005) They are not stealthy in the heart: embryonic stem cells trigger cell infiltration, humoral and T-lymphocyte-based host immune response. Eur J Cardiothorac Surg 28:461–466PubMedCrossRefGoogle Scholar
  23. 23.
    Swijnenburg RJ et al (2005) Embryonic stem cell immunogenicity increases upon differentiation after transplantation into ischemic myocardium. Circulation 112:I166–I172PubMedGoogle Scholar
  24. 24.
    Nussbaum J et al (2007) Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response. FASEB J 21:1345–1357PubMedCrossRefGoogle Scholar
  25. 25.
    Robertson NJ et al (2007) Embryonic stem cell-derived tissues are immunogenic but their inherent immune privilege promotes the induction of tolerance. Proc Natl Acad Sci U S A 104:20920–20925PubMedCrossRefGoogle Scholar
  26. 26.
    Swijnenburg RJ et al (2008) Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts. Proc Natl Acad Sci U S A 105:12991–12996PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Stanford University School of Medicine, Lorrey I Lokey Stem Cell Research BuildingStanfordUSA

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