Top

Journal of Cardiovascular Translational Research

Published in:

01-03-2009

Immunogenicity and Allogenicity: A Challenge of Stem Cell Therapy

Authors: Dominique Charron, Caroline Suberbielle-Boissel, Reem Al-Daccak

Published in: Journal of Cardiovascular Translational Research | Issue 1/2009

Abstract

As age progresses, the regenerative power of one’s own pluripotent stem cells is often inadequate to sustain normal tissue function. Consequently, the incidence of chronic and degenerative diseases has significantly increased. The derivation of adult tissues and organs from a variety of stem cell sources represents the starting mark for regenerative medicine. It is currently considered a developing mean to repair, restore, maintain, or enhance organ functioning through life span. Recent advances in human embryonic stem cells (hESC) research, however, made the prospect of cell replacement therapy even more compelling and highlighted hESC as a fast track in the therapeutic hope. Among the hurdles which have been largely overlooked in the excitement over the expected benefit is the immunogenicity. Indeed, beyond the clear need to establish the safety of hESC and their derived tissues in terms of tumorogenicity and potential to transmit infections, the challenge is to overcome the immunological barriers to their transplantation.

Behfar, A., Perez-Terzic, C., Faustino, R. S., Arrell, D. K., Hodgson, D. M., Yamada, S., et al. (2007). Cardiopoietic programming of embryonic stem cells for tumor-free heart repair. Journal of Experimental Medicine, 204(2), 405–420.PubMedCrossRef

Fenno, L. E., Ptaszek, L. M., & Cowan, C. A. (2008). Human embryonic stem cells: emerging technologies and practical applications. Current Opinion in Genetics & Development 18, 1–6.CrossRef

Jiang, Y., Jahagirdar, B. N., Reinhardt, R. L., Schwartz, R. E., Keene, C. D., Ortiz-Gonzalez, X. R., et al. (2002). Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 418(6893), 41–49.PubMedCrossRef

Bajada, S., Mazakova, I., Richardson, J. B., & Ashammakhi, N. (2008). Updates on stem cells and their applications in regenerative medicine. Journal of Tissue Engineering and Regenerative Medicine, 2(4), 169–183.PubMedCrossRef

Bradley, J. A., Bolton, E. M., & Pedersen, R. A. (2002). Stem cell medicine encounters the immune system. Nature Reviews Immunology, 2(11), 859–871.PubMedCrossRef

Drukker, M., Katchman, H., Katz, G., Even-Tov Friedman, S., Shezen, E., Hornstein, E., et al. (2006). Human embryonic stem cells and their differentiated derivatives are less susceptible to immune rejection than adult cells. Stem Cells, 24(2), 221–229.PubMedCrossRef

Kofidis, T., deBruin, J. L., Tanaka, M., Zwierzchoniewska, M., Weissman, I., Fedoseyeva, E., et al. (2005). They are not stealthy in the heart: embryonic stem cells trigger cell infiltration, humoral and T-lymphocyte-based host immune response. European Journal of Cardio-thoracic Surgery, 28(3), 461–466.PubMedCrossRef

Swijnenburg, R. J., Tanaka, M., Vogel, H., Baker, J., Kofidis, T., Gunawan, F., et al. (2005). Embryonic stem cell immunogenicity increases upon differentiation after transplantation into ischemic myocardium. Circulation, 112(9 Suppl), I166–172.PubMed

Gloor, J., Cosio, F., Lager, D. J., & Stegall, M. D. (2008). The spectrum of antibody-mediated renal allograft injury: Implications for treatment. American Journal of Transplantation, 8(7), 1367–1373.PubMedCrossRef

10.

Terasaki, P. I., & Cai, J. (2005). Humoral theory of transplantation: Further evidence. Current Opinion in Immunology, 17(5), 541–545.PubMed

11.

Koestner, S. C., Kappeler, A., Schaffner, T., Carrel, T. P., Nydegger, U. E., & Mohacsi, P. (2004). Histo-blood group type change of the graft from B to O after ABO mismatched heart transplantation. Lancet, 363(9420), 1523–1525.PubMedCrossRef

12.

Breimer, M. E., Molne, J., Norden, G., Rydberg, L., Thiel, G., & Svalander, C. T. (2006). Blood group A and B antigen expression in human kidneys correlated to A1/A2/B, Lewis, and secretor status. Transplantation, 82(4), 479–485.PubMedCrossRef

13.

Rydberg, L., Skogsberg, U., & Molne, J. (2007). ABO antigen expression in graft tissue: Is titration against donor erythrocytes relevant? Transplantation, 84(12 Suppl), S10–S12.PubMed

14.

Galili, U., Anaraki, F., Thall, A., Hill-Black, C., & Radic, M. (1993). One percent of human circulating B lymphocytes are capable of producing the natural anti-Gal antibody. Blood, 82(8), 2485–2493.PubMed

15.

Cooper, D. K. (1990). Clinical survey of heart transplantation between ABO blood group-incompatible recipients and donors. Journal of Heart Transplantation, 9(4), 376–381.PubMed

16.

Borderie, V. M., Lopez, M., Vedie, F., & Laroche, L. (1997). ABO antigen blood-group compatibility in corneal transplantation. Cornea, 16(1), 1–6.PubMedCrossRef

17.

Ceppellini, R., Bigliani, S., Curtoni, E. S., & Leigheb, G. (1969). Experimental allotransplantation in man. II. The role of A 1, A 2, and B antigens. 3. Enhancement by circulating antibody. Transplantation Proceedings, 1(1), 390–394.PubMed

18.

Genberg, H., Kumlien, G., Wennberg, L., Berg, U., & Tyden, G. (2008). ABO-incompatible kidney transplantation using antigen-specific immunoadsorption and rituximab: A 3-year follow-up. Transplantation, 85(12), 1745–1754.PubMedCrossRef

19.

West, L. J., Pollock-Barziv, S. M., Lee, K. J., Dipchand, A. I., Coles, J. G., & Ruiz, P. (2001). Graft accommodation in infant recipients of ABO-incompatible heart transplants: Donor ABH antigen expression in graft biopsies. Journal of Heart and Lung Transplantation, 20(2), 222.PubMedCrossRef

20.

Cailhier, J. F., Laplante, P., & Hebert, M. J. (2006). Endothelial apoptosis and chronic transplant vasculopathy: Recent results, novel mechanisms. Ameraican Journal of Transplantation, 6(2), 247–253.CrossRef

21.

Reed, E. F. (2003). Signal transduction via MHC class I molecules in endothelial and smooth muscle cells. Critical Reviews in Immunology, 23(1–2), 109–128.PubMedCrossRef

22.

Zou, Y., Stastny, P., Susal, C., Dohler, B., & Opelz, G. (2007). Antibodies against MICA antigens and kidney-transplant rejection. New England Journal of Medicine, 357(13), 1293–1300.PubMedCrossRef

23.

Takemoto, S., Port, F. K., Claas, F. H., & Duquesnoy, R. J. (2004). HLA matching for kidney transplantation. Human Immunology, 65(12), 1489–1505.PubMedCrossRef

24.

Drukker, M., Katz, G., Urbach, A., Schuldiner, M., Markel, G., Itskovitz-Eldor, J., et al. (2002). Characterization of the expression of MHC proteins in human embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 99(15), 9864–9869.PubMedCrossRef

25.

Charron, D. (2005). Immunogenetics today: HLA, MHC and much more. Current Opinion in Immunology, 17(5), 493–497.PubMedCrossRef

26.

Dickinson, A. M., & Charron, D. (2005). Non-HLA immunogenetics in hematopoietic stem cell transplantation. Current Opinion in Immunology, 17(5), 517–525.PubMed

27.

Fairchild, P. J., Robertson, N. J., Minger, S. L., & Waldmann, H. (2007). Embryonic stem cells: Protecting pluripotency from alloreactivity. Current Opinion in Immunology, 19(5), 596–602.PubMedCrossRef

28.

Gould, D. S., & Auchincloss Jr., H. (1999). Direct and indirect recognition: The role of MHC antigens in graft rejection. Immunology Today, 20(2), 77–82.PubMedCrossRef

29.

Fairchild, P. J., Cartland, S., Nolan, K. F., & Waldmann, H. (2004). Embryonic stem cells and the challenge of transplantation tolerance. Trends in Immunology, 25(9), 465–470.PubMedCrossRef

30.

Wang, Z. Z., Au, P., Chen, T., Shao, Y., Daheron, L. M., Bai, H., et al. (2007). Endothelial cells derived from human embryonic stem cells form durable blood vessels in vivo. Nature Biotechnology, 25(3), 317–318.PubMedCrossRef

31.

Kreisel, D., Krupnick, A. S., Gelman, A. E., Engels, F. H., Popma, S. H., Krasinskas, A. M., et al. (2002). Non-hematopoietic allograft cells directly activate CD8+ T cells and trigger acute rejection: An alternative mechanism of allorecognition. Nature Medicine, 8(3), 233–239.PubMedCrossRef

32.

Drukker, M., & Benvenisty, N. (2004). The immunogenicity of human embryonic stem-derived cells. Trends in Biotechnology, 22(3), 136–141.PubMedCrossRef

33.

Gebel, H. M., & Bray, R. A. (2008). Approaches for transplanting the sensitized patient: Biology versus pharmacology. Nephrology Dialysis Transplantation, 23(8), 2454–2457.CrossRef

34.

Duquesnoy, R. J., Howe, J., & Takemoto, S. (2003). HLAmatchmaker: A molecularly based algorithm for histocompatibility determination. IV. An alternative strategy to increase the number of compatible donors for highly sensitized patients. Transplantation, 75(6), 889–897.PubMedCrossRef

35.

Bray, R. A., Nolen, J. D., Larsen, C., Pearson, T., Newell, K. A., Kokko, K., et al. (2006). Transplanting the highly sensitized patient: The emory algorithm. American Journal of Transplantation, 6(10), 2307–2315.PubMedCrossRef

36.

Taylor, C. J., Bolton, E. M., Pocock, S., Sharples, L. D., Pedersen, R. A., & Bradley, J. A. (2005). Banking on human embryonic stem cells: estimating the number of donor cell lines needed for HLA matching. Lancet, 366(9502), 2019–2025.PubMedCrossRef

37.

Rao, M. S., & Auerbach, J. M. (2006). Estimating human embryonic stem-cell numbers. Lancet, 367(9511), 650.PubMedCrossRef

38.

Grusby, M. J., Auchincloss Jr., H., Lee, R., Johnson, R. S., Spencer, J. P., Zijlstra, M., et al. (1993). Mice lacking major histocompatibility complex class I and class II molecules. Proceedings of the National Academy of Sciences of the United States of America, 90(9), 3913–3917.PubMedCrossRef

39.

Byrne, J. A. (2008). Generation of isogenic pluripotent stem cells. Human Molecular Genetics, 17(R1), R37–R41.PubMedCrossRef

40.

Wakayama, T., Tabar, V., Rodriguez, I., Perry, A. C., Studer, L., & Mombaerts, P. (2001). Differentiation of embryonic stem cell lines generated from adult somatic cells by nuclear transfer. Science, 292(5517), 740–743.PubMedCrossRef

41.

Wang, L., Duan, E., Sung, L. Y., Jeong, B. S., Yang, X., & Tian, X. C. (2005). Generation and characterization of pluripotent stem cells from cloned bovine embryos. Biology of Reproduction, 73(1), 149–155.PubMedCrossRef

42.

Drukker, M. (2008). Recent advancements towards the derivation of immune-compatible patient-specific human embryonic stem cell lines. Seminars in Immunology, 20(2), 123–129.PubMedCrossRef

43.

Fandrich, F., Lin, X., Chai, G. X., Schulze, M., Ganten, D., Bader, M., et al. (2002). Preimplantation-stage stem cells induce long-term allogeneic graft acceptance without supplementary host conditioning. Nature Medicine, 8(2), 171–178.PubMedCrossRef

44.

Tian, X., & Kaufman, D. S. (2008). Differentiation of embryonic stem cells towards hematopoietic cells: progress and pitfalls. Current Opinion in Hematology, 15(4), 312–318.PubMedCrossRef

45.

Worthington, J. E., Martin, S., Al-Husseini, D. M., Dyer, P. A., & Johnson, R. W. (2003). Posttransplantation production of donor HLA-specific antibodies as a predictor of renal transplant outcome. Transplantation, 75(7), 1034–1040.PubMedCrossRef

46.

Lefaucheur, C., Nochy, D., Hill, G. S., Suberbielle-Boissel, C., Antoine, C., Charron, D., & Glotz, D. (2007). Determinants of poor graft outcome in patients with antibody-mediated acute rejection. American Journal of Transplantation, 7(4), 832–841.PubMedCrossRef

47.

Lefaucheur, C., Suberbielle-Boissel, C., Hill, G. S., Nochy, D., Andrade, J., Antoine, C., et al. (2008). Clinical relevance of preformed HLA donor-specific antibodies in kidney transplantation. American Journal of Transplantation, 8(2), 324–331.PubMed

48.

Vaidya, S., Partlow, D., Susskind, B., Noor, M., Barnes, T., & Gugliuzza, K. (2006). Prediction of crossmatch outcome of highly sensitized patients by single and/or multiple antigen bead luminex assay. Transplantation, 82(11), 1524–1528.PubMedCrossRef

49.

Terasaki, P. I., Ozawa, M., & Castro, R. (2007). Four-year follow-up of a prospective trial of HLA and MICA antibodies on kidney graft survival. American Journal of Transplantation, 7(2), 408–415.PubMedCrossRef

50.

Gebel, H. M., Bray, R. A., & Nickerson, P. (2003). Pre-transplant assessment of donor-reactive, HLA-specific antibodies in renal transplantation: Contraindication vs. risk. American Journal of Transplantation, 3(12), 1488–1500.PubMedCrossRef

51.

Piazza, A., Adorno, D., Poggi, E., Borrelli, L., Buonomo, O., Pisani, F., et al. (1998). Flow cytometry crossmatch: A sensitive technique for assessment of acute rejection in renal transplantation. Transplantation Proceedings, 30(5), 1769–1771.PubMedCrossRef

52.

Piazza, A., Borrelli, L., Buonomo, O., Pisani, F., Valeri, M., Torlone, N., et al. (1999). Flow cytometry crossmatch and kidney graft outcome. Transplantation Proceedings, 31(1–2), 314–316.PubMedCrossRef

53.

Zangwill, S., Ellis, T., Stendahl, G., Zahn, A., Berger, S., & Tweddell, J. (2007). Practical application of the virtual crossmatch. Pediatric Transplantation, 11(6), 650–654.PubMedCrossRef

54.

Eckels, D. D. (2008). Solid phase testing in the HLA laboratory: Implications for organ allocation. International Journal of Immunogenetics (in press), May 14.

55.

Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131(5), 861–872.PubMedCrossRef

56.

Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126(4), 663–676.PubMedCrossRef

57.

Okita, K., Ichisaka, T., & Yamanaka, S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature, 448(7151), 313–317.PubMedCrossRef

58.

Dimos, J. T., Rodolfa, K. T., Niakan, K. K., Weisenthal, L. M., Mitsumoto, H., Chung, W., et al. (2008). Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science, 321(5893), 1218–1221.PubMedCrossRef

59.

Nishikawa, S., Goldstein, R. A., & Nierras, C. R. (2008). The promise of human induced pluripotent stem cells for research and therapy. Nature Reviews Molecular Cell Biology, 9(9), 725–729.PubMedCrossRef

60.

Kwan, M. D., & Longaker, M. T. (2008). Regenerative medicine: The next frontier. Transplantation, 86(2), 206–207.PubMed

61.

Sharpless, N. E., & DePinho, R. A. (2007). How stem cells age and why this makes us grow old. Nature Reviews Molecular Cell Biology, 8(9), 703–713.PubMedCrossRef

62.

Larbi, A., Franceschi, C., Mazzatti, D., Solana, R., Wikby, A., & Pawelec, G. (2008). Aging of the immune system as a prognostic factor for human longevity. Physiology (Bethesda), 23, 64–74.

63.

Charron, D. (2007). Autologous white blood cell transfusion: Toward a younger immunity. Human Immunology, 68(10), 805–812.PubMedCrossRef

64.

Schirrmacher, V. (2005). T cell-mediated immunotherapy of metastases: State of the art in 2005. Expert Opinion on Biological Therapy, 5(8), 1051–1068.PubMedCrossRef

65.

Vuk-Pavlovic, S. (2008). Rebuilding immunity in cancer patients. Blood Cells, Molecules & Diseases, 40(1), 94–100.CrossRef

66.

Shurin, M. R., Shurin, G. V., & Chatta, G. S. (2007). Aging and the dendritic cell system: Implications for cancer. Critical Reviews in Oncology/Hematology, 64(2), 90–105.PubMedCrossRef

Title: Immunogenicity and Allogenicity: A Challenge of Stem Cell Therapy
Authors: Dominique Charron
Caroline Suberbielle-Boissel
Reem Al-Daccak
Publication date: 01-03-2009
Publisher: Springer US
Published in: Journal of Cardiovascular Translational Research / Issue 1/2009
Print ISSN: 1937-5387
Electronic ISSN: 1937-5395
DOI: https://doi.org/10.1007/s12265-008-9062-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Immunogenicity and Allogenicity: A Challenge of Stem Cell Therapy

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2009

MicroRNAs Challenge the Status Quo of Therapeutic Targeting

Vulnerable Plaque Imaging—Current Techniques

Bone Marrow Cell Therapy After Acute Myocardial Infarction. Back to Bench, or Ready for an Outcome Trial

Panoramic View of The Fifth International Symposium on Stem Cell Therapy and Applied Cardiovascular Biotechnology, April 2008, Madrid (Spain)

Letter from the Editors

Myocardial Viability in Chronic Ischemic Cardiomyopathy: Similarities and Discordance of Different Diagnostic Approaches