Advertisement

Cell-Based Regenerative Therapies: Role of Major Histocompatibility Complex-1 Antigen

  • Alejandra Negro
  • Cynthia St. Hilaire
  • Manfred Boehm
Chapter
Part of the Stem Cells and Cancer Stem Cells book series (STEM, volume 3)

Abstract

Stem cell-based therapies hold promise for the treatment of various human diseases and disorders but also face hurdles that must be overcome to ensure their therapeutic success. Key issues determining the long-term outcome of stem cell therapies include improvements in the survival, engraftment, proliferation, and regeneration of transplanted cells. Although stem cells possess extensive replicative capacity and pluripotency that can be exploited for therapeutic use (Carpenter et al., 2009), immune rejection of donor cells by the host immune system post-transplantation is one of the most serious obstacles that must be cleared (Chidgey and Boyd, 2008). The majority of donor cell death occurs in the first hours to days after transplantation due to a combination of factors, including lack of matrix support to promote cell survival, exposure of transplanted cells to hypoxia/ischemia in host environment, and immune system-mediated cell death (Robey et al., 2008). Recent data have provided valuable insights as to why a majority of donor stem cells die in vivo, a phenomena that limits the efficacy and therapeutic potential of stem cell-based therapies. The expression of the major histocompatibility complex class I (MHC-I) molecules by donor stem cells has emerged as a key factor in determining whether or not a cell is targeted for host immune-mediated destruction post-transplantation (Bix et al., 1991) (Ma et al., 2010). The expression level of MHC-I not only depends on the source of the stem cells, such as embryonic versus adult stem cell populations, but also on the degree to which the cells have been manipulated prior to transplantation into host (Chidgey and Boyd, 2008). Such variation in MHC-I expression will influence the survival and engraftment potential post-transplantiation. Determining the mechanisms regulating donor graft tolerance by the host will be crucial for advancing the clinical application of stem cell-based therapies.

Keywords

Stem cell therapies Transplantation Cell culture techniques MHC-I Embryonic stem cells Interferon-γ 

References

  1. Au P, Daheron LM, Duda DG, Cohen KS, Tyrrell JA, Lanning RM, Fukumura D, Scadden DT, Jain RK (2008) Differential in vivo potential of endothelial progenitor cells from human umbilical cord blood and adult peripheral blood to form functional long-lasting vessels. Blood 111:1302–1305PubMedCrossRefGoogle Scholar
  2. Bauwens C, Yin T, Dang S, Peerani R, Zandstra PW (2005) Development of a perfusion fed bioreactor for embryonic stem cell-derived cardiomyocyte generation: oxygen-mediated enhancement of cardiomyocyte output. Biotechnol Bioeng 90:452–461PubMedCrossRefGoogle Scholar
  3. Bix M, Liao NS, Zijlstra M, Loring J, Jaenisch R, Raulet D (1991) Rejection of class I MHC-deficient haemopoietic cells by irradiated MHC-matched mice. Nature 349:329–331PubMedCrossRefGoogle Scholar
  4. Bryceson YT, March ME, Ljunggren HG, Long EO (2006) Activation, coactivation, and costimulation of resting human natural killer cells. Immunol Rev 214:73–91PubMedCrossRefGoogle Scholar
  5. Cardone MH, Salvesen GS, Widmann C, Johnson G, Frisch SM (1997) The regulation of anoikis: MEKK-1 activation requires cleavage by caspases. Cell 90:315–323PubMedCrossRefGoogle Scholar
  6. Carpenter MK, Frey-Vasconcells J, Rao MS (2009) Developing safe therapies from human pluripotent stem cells. Nat Biotechnol 27:606–613PubMedCrossRefGoogle Scholar
  7. Chidgey AP, Boyd RL (2008) Immune privilege for stem cells: not as simple as it looked. Cell Stem Cell 3:357–358PubMedCrossRefGoogle Scholar
  8. Drukker M, Katz G, Urbach A, Schuldiner M, Markel G, Itskovitz-Eldor J, Reubinoff B, Mandelboim O, Benvenisty N (2002) Characterization of the expression of MHC proteins in human embryonic stem cells. Proc Natl Acad Sci USA 99:9864–9869PubMedCrossRefGoogle Scholar
  9. Elliott JM, Wahle JA, Yokoyama WM (2010) MHC class I-deficient natural killer cells acquire a licensed phenotype after transfer into an MHC class I-sufficient environment. J Exp Med 207:2073–2079PubMedCrossRefGoogle Scholar
  10. Fandrich F, Lin X, Chai GX, Schulze M, Ganten D, Bader M, Holle J, Huang DS, Parwaresch R, Zavazava N, Binas B (2002) Preimplantation-stage stem cells induce long-term allogeneic graft acceptance without supplementary host conditioning. Nat Med 8:171–178PubMedCrossRefGoogle Scholar
  11. Freimark D, Pino-Grace P, Pohl S, Weber C, Wallrapp C, Geigle P, Portner R, Czermak P (2010) Use of encapsulated stem cells to overcome the bottleneck of cell availability for cell therapy approaches. Transfus Med Hemother 37:66–73PubMedCrossRefGoogle Scholar
  12. Grzywacz B, Miller JS, Verneris MR (2008) Use of natural killer cells as immunotherapy for leukaemia. Best Pract Res Clin Haematol 21:467–483PubMedCrossRefGoogle Scholar
  13. Koch CA, Geraldes P, Platt JL (2008) Immunosuppression by embryonic stem cells. Stem Cells 26:89–98PubMedCrossRefGoogle Scholar
  14. Kovacic JC, Harvey RP, Dimmeler S (2007) Cardiovascular regenerative medicine: digging in for the long haul. Cell Stem Cell 1:628–633PubMedCrossRefGoogle Scholar
  15. Ma M, Ding S, Lundqvist A, San H, Fang F, Konoplyannikov M, Berry C, Beltran LE, Chen G, Kovacic JC, Boehm M (2010) Major histocompatibility complex-I expression on embryonic stem cell-derived vascular progenitor cells is critical for syngeneic transplant survival. Stem Cells 28:1465–1475PubMedCrossRefGoogle Scholar
  16. Meyer D, Thomson G (2001) How selection shapes variation of the human major histocompatibility complex: a review. Ann Hum Genet 65:1–26PubMedCrossRefGoogle Scholar
  17. Mooney DJ, Vandenburgh H (2008) Cell delivery mechanisms for tissue repair. Cell Stem Cell 2:205–213PubMedCrossRefGoogle Scholar
  18. Newman RE, Yoo D, LeRoux MA, Danilkovitch-Miagkova A (2009) Treatment of inflammatory diseases with mesenchymal stem cells. Inflamm Allergy Drug Targets 8:110–123PubMedCrossRefGoogle Scholar
  19. Robey TE, Saiget MK, Reinecke H, Murry CE (2008) Systems approaches to preventing transplanted cell death in cardiac repair. J Mol Cell Cardiol 45:567–581PubMedCrossRefGoogle Scholar
  20. Ryan JM, Barry FP, Murphy JM, Mahon BP (2005) Mesenchymal stem cells avoid allogeneic rejection. J Inflamm (Lond) 2:8CrossRefGoogle Scholar
  21. Skuk D, Paradis M, Goulet M, Tremblay JP (2007) Ischemic central necrosis in pockets of transplanted myoblasts in nonhuman primates: implications for cell-transplantation strategies. Transplantation 84:1307–1315PubMedCrossRefGoogle Scholar
  22. Sun C, Zhang H, Li J, Huang H, Cheng H, Wang Y, Li P, An Y (2010) Modulation of the major histocompatibility complex by neural stem cell-derived neurotrophic factors used for regenerative therapy in a rat model of stroke. J Transl Med 8:77PubMedCrossRefGoogle Scholar
  23. Swijnenburg RJ, Tanaka M, Vogel H, Baker J, Kofidis T, Gunawan F, Lebl DR, Caffarelli AD, de Bruin JL, Fedoseyeva EV, Robbins RC (2005) Embryonic stem cell immunogenicity increases upon differentiation after transplantation into ischemic myocardium. Circulation 112:1166–1172Google Scholar
  24. Swijnenburg RJ, Schrepfer S, Cao F, Pearl JI, Xie X, Connolly AJ, Robbins RC, Wu JC (2008a) In vivo imaging of embryonic stem cells reveals patterns of survival and immune rejection following transplantation. Stem Cells Dev 17:1023–1029PubMedCrossRefGoogle Scholar
  25. Swijnenburg RJ, Schrepfer S, Govaert JA, Cao F, Ransohoff K, Sheikh AY, Haddad M, Connolly AJ, Davis MM, Robbins RC, Wu JC (2008b) Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts. Proc Natl Acad Sci USA 105:12991–12996PubMedCrossRefGoogle Scholar
  26. Tolar J, O’Shaughnessy MJ, Panoskaltsis-Mortari A, McElmurry RT, Bell S, Riddle M, McIvor RS, Yant SR, Kay MA, Krause D, Verfaillie CM, Blazar BR (2006) Host factors that impact the biodistribution and persistence of multipotent adult progenitor cells. Blood 107:4182–4188PubMedCrossRefGoogle Scholar
  27. Vaananen HK (2005) Mesenchymal stem cells. Ann Med 37:469–479PubMedCrossRefGoogle Scholar
  28. Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, Yokoyama WM, Ugolini S (2011) Innate or adaptive immunity? The example of natural killer cells. Science 331:44–49PubMedCrossRefGoogle Scholar
  29. Yokoyama WM (2008) Mistaken notions about natural killer cells. Nat Immunol 9:481–485PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Alejandra Negro
    • 1
  • Cynthia St. Hilaire
    • 1
  • Manfred Boehm
    • 1
  1. 1.Center for Molecular Medicine, National Heart, Lung, and Blood InstituteBethesdaUSA

Personalised recommendations