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New Strategies in Composite Tissue Allotransplantation

  • Gerald Brandacher
  • Maria Chicco
  • W. P. Andrew Lee
Chapter

Abstract

Over the last two decades, composite tissue allotransplantation (CTA), more recently referred to as vascularized composite allotransplantation (VCA), has become a valid therapeutic and restorative option for patients with severe tissue defects. While functional outcomes are such that recipients’ quality of life is significantly improved and in some cases even dramatically enhanced, long-term risks are still difficult to evaluate in a precise fashion. Strategies have been devised, and new ones are being explored, in order to minimize or, if possible, eliminate the need for immunosuppression while keeping rejection under control. Success in these efforts would ultimately tilt the risk versus benefit balance, so that VCA may become widely adopted and a standard therapeutic option. This chapter introduces a brief historical perspective as well as a description of the current state of play within the discipline. It examines emerging challenges and then focuses on novel research avenues and clinical perspectives for the future.

References

  1. 1.
    Albersen, M. (2016). Getting ready for penile transplantation. European Urology, 71(4), 594–595. Available online at: http://dx.doi.org/10.1016/j.eururo.2016.10.025. Accessed on 31st Oct 2016.CrossRefPubMedGoogle Scholar
  2. 2.
    Balayla, J. (2016). Uterine transplants in the Canadian setting: A theoretical framework. Journal of Obstetrics and Gynaecology Canada, 38, 955–960.CrossRefPubMedGoogle Scholar
  3. 3.
    Barth, R. N., Rodriguez, E. D., Mundinger, G. S., Nam, A. J., Ha, J. S., Hui-Chou, H., Jones, L. S., Panda, A., Shipley, S. T., Drachenberg, C. B., Kukuruga, D., & Bartlett, S. T. (2011). Vascularized bone marrow-based immunosuppression inhibits rejection of vascularized composite allografts in nonhuman primates. American Journal of Transplantation, 11, 1407–1416.CrossRefPubMedGoogle Scholar
  4. 4.
    Billingham, R. E., Brent, L., & Medawar, P. B. (1953). Activity acquired tolerance of foreign cells. Nature, 172, 603–606.CrossRefPubMedGoogle Scholar
  5. 5.
    Brandacher, G., Lee, W. P., & Schneeberger, S. (2012). Minimizing immunosuppression in hand transplantation. Expert Review of Clinical Immunology, 8, 673–683.CrossRefPubMedGoogle Scholar
  6. 6.
    Brännström, M., Johannesson, L., Dahm-Kähler, P., Enskog, A., Mölne, J., Kvarnström, N., Diaz-Garcia, C., Hanafy, A., Lundmark, C., Marcickiewicz, J., Gäbel, M., Groth, K., Akouri, R., Eklind, S., Holgersson, J., Tzakis, A., & Olausson, M. (2014). First clinical uterus transplantation trial: A six-month report. Fertility and Sterility, 101, 1228–1236.CrossRefPubMedGoogle Scholar
  7. 7.
    Brännström, M., Johannesson, L., Bokström, H., Kvarnström, N., Mölne, J., Dahm-Kähler, P., Enskog, A., Milenkovic, M., Ekberg, J., Diaz-Garcia, C., Gäbel, M., Hanafy, A., Hagberg, H., Olausson, M., & Nilsson, L. (2015). Livebirth after uterus transplantation. Lancet, 385, 607–616.CrossRefPubMedGoogle Scholar
  8. 8.
    Carty, M. J., Zuker, R., Cavadas, P., Pribaz, J. J., Talbot, S. G., & Pohamac, B. (2013). The case for lower extremity allotransplantation. Plastic and Reconstructive Surgery, 131, 1272–1277.CrossRefPubMedGoogle Scholar
  9. 9.
    Cendales, L. C., Kanitakis, J., Schneeberger, S., Burns, C., Ruiz, P., Landin, L., Remmelink, M., Hewitt, C. W., Landgren, T., Lyon, B., Drachenberg, C. B., Solez, K., Kirk, A. D., Kleiner, D. E., & Racusen, L. (2008). The Banff 2007 working classification of skin-containing composite tissue allograft pathology. American Journal of Transplantation, 8, 1396–1400.CrossRefPubMedGoogle Scholar
  10. 10.
    Cetrulo, C. L., Jr., Drijkoningen, T., & Sachs, D. H. (2015). Tolerance induction via mixed chimerism in vascularized composite allotransplantation: Is it time for clinical application? Current Opinion in Organ Transplantation, 20, 602–607.CrossRefPubMedGoogle Scholar
  11. 11.
    Chandraker, A., Arscott, R., Murphy, G. F., Lian, C. G., Bueno, E. M., Marty, F. M., Rennke, H. G., Milford, E., Tullius, S. G., & Pomahac, B. (2014). The management of antibody-mediated rejection in the first presensitized recipient of a full-face allotransplant. American Journal of Transplantation, 14, 1446–1452.CrossRefPubMedGoogle Scholar
  12. 12.
    Chen, B., Hong, X., Corbin, D. R., & Ildstad, S. T. (2012). A clinically feasible approach to induce delayed tolerance in recipients of prior kidney or vascularized composite allotransplants. Transplantation, 94, 671–678.CrossRefPubMedGoogle Scholar
  13. 13.
    Chhabra, A., Ring, A. M., Weiskopf, K., Schnorr, P. G., Gordon, S., Le, A. C., Kwon, H. S., Ring, N. G., Volkmer, J., Ho, P. H., Tseng, S., Weissman, I. L., & Shizuru, J. A. (2016). Hematopoietic stem cell transplantation in immunocompetent hosts without radiation or chemotherapy. Science Translational Medicine, 8, 351ra105.CrossRefPubMedGoogle Scholar
  14. 14.
    Cooney, D. S., Wimmers, E. G., Ibrahim, Z., Grahammer, J., Christensen, J. M., Brat, G. A., Wu, L. W., Sarhane, K. A., Lopez, J., Wallner, C., Furtmüller, G. J., Yuan, N., Pang, J., Sarkar, K., Lee, W. P., & Brandacher, G. (2016). Mesenchymal stem cells enhance nerve regeneration in a rat sciatic nerve repair and hindlimb transplant model. Scientific Reports, 6, 31306. Available online at: doi: 10.1038/srep31306. Accessed on 31st Oct 2016.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Del Bene, M., Peri Di Caprio, A., Melzi, M. L., Pioltelli, P. E., & Bonomi, S. (2013). Autologous mesenchymal stem cells as a new strategy in immunosuppressant therapy in double hand allotransplantation. Plastic and Reconstructive Surgery, 131, 305–307.CrossRefGoogle Scholar
  16. 16.
    Department of Health and Human Services. (2013). Final rule: Organ procurement and transplantation network. Published online July 3rd 2013. Available at: https://www.gpo.gov/fdsys/pkg/FR-2013-07-03/html/2013-15731.htm. Accessed on 31st Oct 2016.
  17. 17.
    Diefenbeck, M., Nerlich, A., Schneeberger, S., Wagner, F., & Hofmann, G. O. (2011). Allograft vasculopathy after allogeneic vascularized knee transplantation. Transplant International, 24, 1–5.CrossRefGoogle Scholar
  18. 18.
    Dubernard, J. M., Owen, E., Lefrançois, N., Petruzzo, P., Martin, X., Dawahre, M., Jullien, D., Kanitakis, J., Frances, C., Preville, X., Gebuhrer, L., Hakim, N., Lanzetta, M., Kapila, H., Herzberg, G., & Revillard, J. (2000). First human hand transplantation. Transplant International, 13, 521–524.Google Scholar
  19. 19.
    Dubernard, J. M., Lengelé, B., Morelon, E., Testelin, S., Badet, L., Moure, C., Beziat, J. L., Dakpé, S., Kanitakis, J., D’Hauthuille, C., El Jaafari, A., Petruzzo, P., Lefrancois, N., Taha, F., Sirigu, A., Di Marco, G., Carmi, E., Bachmann, D., Cremades, S., Giraux, P., Burloux, G., Hequet, O., Parquet, N., Francès, C., Michallet, M., Martin, X., & Devauchelle, B. (2007). Outcomes 18 months after the first human partial face transplantation. The New England Journal of Medicine, 357, 2451–2460.CrossRefPubMedGoogle Scholar
  20. 20.
    Eljaafari, A., Badet, L., Kanitakis, J., Ferrand, C., Farre, A., Petruzzo, P., Morelon, E., Dubosson, M., Tiberghien, P., Dubois, V., Martin, X., Miossec, P., & Dubernard, J. M. (2006). Isolation of regulatory T cells in the skin of a human hand-allograft, up to six years posttransplantation. Transplantation, 82, 1764–1768.CrossRefPubMedGoogle Scholar
  21. 21.
    Faroni, A., Mobasseri, S. A., Kingham, P. J., & Reid, A. J. (2015). Peripheral nerve regeneration: experimental strategies and future perspectives. Advanced Drug Delivery Reviews, 82, 160–167.CrossRefPubMedGoogle Scholar
  22. 22.
    Fryer, M., Grahammer, J., Khalifian, S., Furtmüller, G. J., Lee, W. P., Raimondi, G., & Brandacher, G. (2015). Exploring cell-based tolerance strategies for hand and face transplantation. Expert Review of Clinical Immunology, 11, 1189–1204.CrossRefPubMedGoogle Scholar
  23. 23.
    Fukushima, N., & Ohkawa, H. (1995). Hematopoietic stem cells and microenvironment: The proliferation and differentiation of stromal cells. Critical Reviews in Oncology/Hematology, 20, 255–270.CrossRefPubMedGoogle Scholar
  24. 24.
    Furtmüller, G., Crane, N., Luthra, R., Swanson, E., Cheng, H, T., Oh, B., Fryer, M., Elster, E., Lee, W., Brandacher, G. (2015). Non-invasive imaging modalities for immune monitoring of vascularized composite allografts using a translational large animal model. Abstract presented at 2015. American Transplant Congress. Available online at: http://www.atcmeetingabstracts.com/abstract/non-invasive-imaging-modalities-for-immune-monitoring-of-vascularized-composite-allografts-using-a-translational-large-animal-model/. Accessed on 31st Oct 2016.
  25. 25.
    Gajanayake, T., Olariu, R., Leclère, F. M., Dhayani, A., Yang, Z., Bongoni, A. K., Banz, Y., Constantinescu, M. A., Karp, J. M., Vemula, P. K., Rieben, R., & Vögelin, E. (2014). A single localized dose of enzyme-responsive hydrogel improves long-term survival of a vascularized composite allograft. Science Translational Medicine, 6, 249ra110.CrossRefPubMedGoogle Scholar
  26. 26.
    Geissler, E. K. (2012). The ONE Study compares cell therapy products in organ transplantation: introduction to a review series on suppressive monocyte-derived cells. Transplantation Research, 1, 10–12.CrossRefGoogle Scholar
  27. 27.
    Gilbert, R. (1964). Hand transplanted from a cadaver is reamputated. Medical Tribune and Medical News, 5, 23.Google Scholar
  28. 28.
    Gorantla, V. S., Brandacher, G., Schneeberger, S., Zheng, X. X., Donnenberg, A. D., Losee, J. E., & Lee, W. P. (2011). Favoring the risk-benefit balance for upper extremity transplantation – The Pittsburgh Protocol. Hand Clinics, 27, 511–520.CrossRefPubMedGoogle Scholar
  29. 29.
    Hequet, O., Morelon, E., Bourgeot, J. P., Dubois, V., Devauchelle, B., Dubernard, J. M., & Michallet, M. (2008). Allogeneic donor bone marrow cells recovery and infusion after allogeneic face transplantation from the same donor. Bone Marrow Transplantation, 41, 1059–1061.CrossRefPubMedGoogle Scholar
  30. 30.
    Hu, W., Lu, J., Zhang, L., Wu, W., Nie, H., Zhu, Y., Deng, Z., Zhao, Y., Sheng, W., Chao, Q., Qiu, X., Yang, J., & Bai, Y. (2006). A preliminary report of penile transplantation. European Urology, 50, 851–853.CrossRefPubMedGoogle Scholar
  31. 31.
    Huet, S., Tardieu, A., Filloux, M., Essig, M., Pichon, N., Therme, J. F., Piver, P., Aubard, Y., Ayoubi, J. M., Garbin, O., Collinet, P., Agostini, A., Lavoue, V., Piccardo, A., & Gauthier, T. (2016). Uterus transplantation in France: for which patients? European Journal of Obstetrics & Gynecology and Reproductive Biology, 205, 7–10.CrossRefGoogle Scholar
  32. 32.
    Issa, F., & Wood, K. J. (2014). The potential role for regulatory T-cell therapy in vascularized composite allograft transplantation. Current Opinion in Organ Transplantation, 19, 558–565.CrossRefPubMedGoogle Scholar
  33. 33.
    Jones, N. F. (2002). Concerns about human hand transplantation in the 21st century. The Journal of Hand Surgery, 27, 771–787.CrossRefPubMedGoogle Scholar
  34. 34.
    Jones, N. F., & Schneeberger, S. (2009). Arm transplantation: Prospects and visions. Transplantation Proceedings, 41, 476–480.CrossRefPubMedGoogle Scholar
  35. 35.
    Kanitakis, J., Jullien, D., Petruzzo, P., Hakim, N., Claudy, A., Revillard, J. P., Owen, E., & Dubernard, J. M. (2003). Clinicopathological features of graft rejection of the first hand allograft. Transplantation, 76, 688–693.CrossRefPubMedGoogle Scholar
  36. 36.
    Kanitakis, J., Petruzzo, P., Badet, L., Gazarian, A., Thaunat, O., Testelin, S., Devauchelle, B., Dubernard, J. M., & Morelon, E. (2016). Chronic rejection in human vascularized composite allotransplantation (hand and face recipients): An update. Transplantation, 10, 2053–2061.CrossRefGoogle Scholar
  37. 37.
    Kaufman, C. L., Ouseph, R., Blair, B., Kutz, J. E., Tsai, T. M., Scheker, L. R., Tien, H. Y., Moreno, R., Ozyurekoglu, T., Banegas, R., Murphy, E., Burns, C. B., Zaring, R., Cook, D. F., & Marvin, M. R. (2012). Graft vasculopathy in clinical hand transplantation. American Journal of Transplantation, 12, 1004–1016.CrossRefPubMedGoogle Scholar
  38. 38.
    Kawai, T., Cosimi, A. B., Spitzer, T. R., Tolkoff-Rubin, N., Suthanthiran, M., Saidman, S. L., Shaffer, J., Preffer, F. I., Ding, R., Sharma, V., Fishman, J. A., Dey, B., Ko, D. S., Hertl, M., Goes, N. B., Wong, W., Williams, W. W., Jr., Colvin, R. B., Sykes, M., & Sachs, D. H. (2008). HLA-mismatched renal transplantation without maintenance immunosuppression. The New England Journal of Medicine, 358, 353–361.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Kawai, T., Sachs, D. H., Sprangers, B., Spitzer, T. R., Saidman, S. L., Zorn, E., Tolkoff-Rubin, N., Preffer, F., Crisalli, K., Gao, B., Wong, W., Morris, H., LoCascio, S. A., Sayre, P., Shonts, B., Williams, W. W., Smith, R. N., Colvin, R. B., Sykes, M., & Cosimi, A. B. (2014). Long-term results in recipients of combined HLA-mismatched kidney and bone marrow transplantation without maintenance immunosuppression. American Journal of Transplantation, 14, 1599–1611.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Koga, H., Yamataka, A., Wang, K., Kato, Y., Lane, G. J., Kobayashi, H., Sueyoshi, N., & Miyano, T. (2003). Experimental allogenic penile transplantation. Journal of Pediatric Surgery, 38, 1802–1805.CrossRefPubMedGoogle Scholar
  41. 41.
    Lee, W. P., Yaremchuk, M. J., Pan, Y. C., Randolph, M. A., Tan, C. M., & Weiland, A. J. (1991). Relative antigenicity of components of a vascularized limb allograft. Plastic and Reconstructive Surgery, 87, 401–411.CrossRefPubMedGoogle Scholar
  42. 42.
    Leto Barone, A. A., Sun, Z., Montgomery, R. A., Lee, W. P., & Brandacher, G. (2013). Impact of donor-specific antibodies in reconstructive transplantation. Expert Review of Clinical Immunology, 9, 835–844.CrossRefPubMedGoogle Scholar
  43. 43.
    Leventhal, J., Abecassis, M., Miller, J., Gallon, L., Tollerud, D., Elliott, M. J., Bozulic, L. D., Houston, C., Sustento-Reodica, N., & Ildstad, S. T. (2013). Tolerance induction in HLA disparate living donor kidney transplantation by donor stem cell infusion: Durable chimerism predicts outcome. Transplantation, 95, 169–176.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Levitsky, J. (2011). Operational tolerance: Past lessons and future prospects. Liver Transplantation, 17, 222–232.CrossRefPubMedGoogle Scholar
  45. 45.
    Lin, C. H., Wang, Y. L., Anggelia, M. R., Chuang, W. Y., Cheng, H. Y., Mao, Q., Zelken, J. A., Lin, C. H., Zheng, X. X., Lee, W. P. A., & Brandacher, G. (2016). Combined Anti-CD154/CTLA4Ig costimulation blockade-based therapy induces donor-specific tolerance to vascularized osteomyocutaneous allografts. American Journal of Transplantation, 16, 2030–2041.CrossRefPubMedGoogle Scholar
  46. 46.
    Liu, G., Cheng, Y., Guo, S., Feng, Y., Li, Q., Jia, H., Wang, Y., Tong, L., & Tong, X. (2011). Transplantation of adipose-derived stem cells for peripheral nerve repair. International Journal of Molecular Medicine, 28, 565–572.PubMedGoogle Scholar
  47. 47.
    Mathes, D. W., Randolph, M. A., Solari, M. G., Nazzal, J. A., Nielsen, G. P., Arn, J. S., Sachs, D. H., & Lee, W. P. (2003). Split tolerance to a composite tissue allograft in a swine model. Transplantation, 15, 25–31.CrossRefGoogle Scholar
  48. 48.
    Medawar, P. B. (1944). The behaviour and fate of skin autografts and skin homografts in rabbits: A report to the War Wounds Committee of the Medical Research Council. Journal of Anatomy, 78, 176–199.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Medawar, P. B. (1945). A second study of the behaviour and fate of skin homografts in rabbits: A report to the War Wounds Committee of the Medical Research Council. Journal of Anatomy, 79, 157–176.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Morelon, E., Kanitakis, J., & Petruzzo, P. (2012). Immunological issues in clinical composite tissue allotransplantation: Where do we stand today? Transplantation, 93, 855–859.CrossRefPubMedGoogle Scholar
  51. 51.
    Morelon, E., Kanitakis, J., Petruzzo, P., Badet, L., & Thaunat, O. (2015). Immunological challenges in vascularised composite allotransplantation. Current Transplantation Reports, 2, 276–283.CrossRefGoogle Scholar
  52. 52.
    Mundinger, G. S., Nam, A. J., Hui-Chou, H. G., Stanwix, M. G., Jones, L. S., Drachenberg, C. B., Kukuruga, D., Shipley, S. T., Dorafshar, A. H., Panda, A., Bartlett, S. T., Bart, R. N., & Rodriguez, E. D. (2011). Nonhuman primate model of fibula vascularized composite tissue allotransplantation demonstrates donor-recipient bony union. Plastic and Reconstructive Surgery, 128, 1193–1204.CrossRefPubMedGoogle Scholar
  53. 53.
    Mundinger, G. S., Munivenkatappa, R., Drachenberg, C. B., Ha, J. S., Vaca, E. E., Shipley, S. T., Papadimitriou, J. C., Bartlett, S. T., Rodriguez, E. D., & Barth, R. N. (2013). Histopathology of chronic rejection in a nonhuman primate model of vascularized composite allotransplantation. Transplantation, 95, 1204–1210.CrossRefPubMedGoogle Scholar
  54. 54.
    Organ Procurement and Transplantation Network. (2015). VCA from living donors. Published online on 2nd June 2015. Available at: https://optn.transplant.hrsa.gov/resources/by-organ/vascular-composite-allograft/vcas-from-living-donors/. Accessed on 31st Oct 2016.
  55. 55.
    Pascual, M., Theruvath, T., Kawai, T., Tolkoff-Rubin, N., & Cosimi, A. B. (2002). Strategies to improve long-term outcomes after renal transplantation. The New England Journal of Medicine, 346, 580–590.CrossRefPubMedGoogle Scholar
  56. 56.
    Petruzzo, P., Lanzetta, M., Dubernard, J. M., Landin, L., Cavadas, P., Margreiter, R., Schneeberger, S., Breidenbach, W., Kaufman, C., Jablecki, J., Schuind, D., & Dumontier, C. (2010). The international registry on hand and composite tissue transplantation. Transplantation, 90, 1590–1594.CrossRefPubMedGoogle Scholar
  57. 57.
    Petruzzo, P., & Dubernard, J. M. (2011). The international registry on hand and composite tissue allotransplantation. Clinical Transplants, 247–253.Google Scholar
  58. 58.
    Petruzzo, P., Kanitakis, J., Badet, L., Pialat, J. B., Boutroy, S., Charpulat, R., Mouly, J., Gazarian, A., Lanzetta, M., Brunet, M., Devauchelle, B., Testelin, S., Martin, X., Dubernard, J. M., & Morelon, E. (2011). Long-term follow-up in composite tissue allotransplantation: In-depth study of five (hand and face) recipients. American Journal of Transplantation, 11, 808–816.CrossRefPubMedGoogle Scholar
  59. 59.
    Petruzzo, P., Testelin, S., Kanitakis, J., Badet, L., Lengelé, B., Girbon, J. P., Parmentier, H., Malcus, C., Morelon, E., Devauchelle, B., & Dubernard, J. M. (2012). First human face transplantation: 5 years outcomes. Transplantation, 93, 236–240.CrossRefPubMedGoogle Scholar
  60. 60.
    Petruzzo, P., Kanitakis, J., Testelin, S., Pialat, J. B., Buron, F., Badet, L., Thaunat, O., Devauchelle, B., & Morelon, E. (2015). Clinicopathological findings of chronic rejection in a face grafted patient. Transplantation, 99, 2644–2650.CrossRefPubMedGoogle Scholar
  61. 61.
    Plock, J. A., Schnider, J. T., Solari, M. G., Zheng, X. X., & Gorantla, V. S. (2013). Perspectives on the use of mesenchymal stem cells in vascularized composite allotransplantation. Frontiers in Immunology, 4, 1–5.Google Scholar
  62. 62.
    Ravindra, K. V., & Ildstad, S. T. (2011). Immunosuppressive protocols and immunological challenges related to hand transplantation. Hand Clinics, 27, 467–479.CrossRefPubMedGoogle Scholar
  63. 63.
    Rudensky, A. Y. (2011). Regulatory T cells and Foxp3. Immunological Reviews, 241, 260–268.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Sachs, D. H., Kawai, T., & Sykes, M. (2014). Induction of tolerance through mixed chimerism. Cold Spring Harbor Perspectives in Medicine, 4, 1–19.CrossRefGoogle Scholar
  65. 65.
    Safinia, N., Vaikunthanathan, T., Fraser, H., Thirkell, S., Lowe, K., Blackmore, L., Whitehouse, G., Martinez-Llordella, M., Jassem, W., Sanchez-Fueyo, A., Lechler, R. I., & Lombardi, G. (2016). Successful expansion of functional and stable regulatory T cells for immunotherapy in liver transplantation. Oncotarget, 7, 7563–7577.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Scandling, J. D., Busquet, S., Dejbakhsh-Jones, S., Benike, C., Sarwal, M., Millan, M. T., Shizuru, J. A., Lowsky, R., Engleman, E. G., & Strober, S. (2012). Tolerance and withdrawal of immunosuppressive drugs in patients given kidney and hematopoietic cell transplants. American Journal of Transplantation, 12, 1133–1145.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Scheib, J., & Höke, A. (2013). Advances in peripheral nerve regeneration. Nature Reviews. Neurology, 9, 668–676.CrossRefPubMedGoogle Scholar
  68. 68.
    Schneeberger, S., Gorantla, V. S., Brandacher, G., Zeevi, A., Demetris, A. J., Lunz, J. G., Metes, D. M., Donnenberg, A. D., Shores, J. T., Dimartini, A. F., Kiss, J. E., Imbriglia, J. E., Azari, K., Goitz, R. J., Manders, E. K., Nguyen, V. T., Cooney, D. S., Wachtman, G. S., Keith, J. D., Fletcher, D. R., Macedo, C., Planinsic, R., Losee, J. E., Shapiro, R., Starzl, T. E., & Lee, A. W. P. (2013). Upper-extremity transplantation using a cell-based protocol to minimize immunosuppression. Annals of Surgery, 257, 345–351.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Schweizer, R., Gorantla, V. S., & Plock, J. A. (2015). Premise and promise of mesenchymal stem cell-based therapies in clinical vascularized composite allotransplantation. Current Opinion in Organ Transplantation, 20, 608–614.CrossRefPubMedGoogle Scholar
  70. 70.
    Setoguchi, K., Kishimoto, H., Kobayashi, S., Shimmura, H., Ishida, H., Toki, D., Suzuki, T., Ohnuki, K., Tate, Y., Fujioka, S., Abe, R., & Tanabe, K. (2010). Potential role of host effector memory CD8+ T cells in marrow rejection after mixed chimerism induction in cynomolgus monkeys. Transplant Immunology, 23, 194–203.CrossRefPubMedGoogle Scholar
  71. 71.
    Seyam, R. M., Kattan, S. A., Assad, L. W., El-Sayed, R. M., & Almohanna, F. H. (2013). Penile autotransplantation in rats: An animal model. Urology Annals, 5, 255–258.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Sopko, N. A., Matsui, H., Lough, D. M., Miller, D., Harris, K., Kates, M., Liu, X., Billups, K., Redett, R., Burnett, A. L., Brandacher, G., & Bivalacqua, T. J. (2017). Ex vivo model of human penile transplantation and rejection: Implications for erectile tissue physiology. European Urology, 71(4), 584–593. Available at: http://dx.doi.org/10.1016/j.eururo.2016.07.006. Aaccessed on 31st Oct 2016.CrossRefPubMedGoogle Scholar
  73. 73.
    Tonsho, M., Lee, S., Aoyama, A., Boskovic, S., Nadazdin, O., Capetta, K., Smith, R. N., Colvin, R. B., Sachs, D. H., Cosimi, A. B., Kawai, T., Madsen, J. C., Benichou, G., & Allan, J. S. (2015). Tolerance of lung allografts achieved in nonhuman primates via mixed hematopoietic chimerism. American Journal of Transplantation, 15, 2231–2239.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Unadkat, J. V., Schneeberger, S., Horibe, E. H., Goldbach, C., Solari, M. G., Washington, K. M., Gorantla, V. S., Cooper, G. M., Thomson, A. W., & Lee, A. W. P. (2010). Composite tissue vasculopathy and degeneration following multiple episodes of acute rejection in reconstructive transplantation. American Journal of Transplantation, 10, 251–261.CrossRefPubMedGoogle Scholar
  75. 75.
    Weissenbacher, A., Hautz, T., Zelger, B., Zelger, B. G., Mayr, V., Brandacher, G., Pratschke, J., & Schneeberger, S. (2013). Antibody-mediated rejection in hand transplantation. Transplant International, 27, 13–17.CrossRefGoogle Scholar
  76. 76.
    Wekerle, T., Kurtz, J., Ito, H., Ronquillo, J. V., Dong, V., Zhao, G., Shaffer, J., Sayegh, M. H., & Sykes, M. (2000). Allogeneic bone marrow transplantation with co-stimulatory blockade induces macrochimerism and tolerance without cytoreductive host treatment. Nature Medicine, 6, 464–469.CrossRefPubMedGoogle Scholar
  77. 77.
    Wiebe, C., & Nickerson, P. (2013). Posttransplant monitoring of de novo human leukocyte antigen donor-specific antibodies in kidney transplantation. Current Opinion in Organ Transplantation, 18, 470–477.CrossRefPubMedGoogle Scholar
  78. 78.
    Wu, S., Xu, H., Ravindra, K., & Ildstad, S. T. (2009). Composite tissue allotransplantation: past, present and future – The history and expanding applications of CTA as a new frontier in transplantation. Transplantation Proceedings, 41, 463–465.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Yamada, Y., Benichou, G., Cosimi, A. B., & Kawai, T. (2012). Tolerance induction after organ transplantation, ‘delayed tolerance’, via the mixed chimerism approach. Chimerism, 3, 24–28.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Yamada, Y., Boskovic, S., Aoyama, A., Murakami, T., Putheti, P., Smith, R. N., Ochiai, T., Nadazdin, O., Koyama, I., Boenisch, O., Najafian, N., Bhasin, M. K., Colvin, R. B., Madsen, J. C., Strom, T. B., Sachs, D. H., Benichou, G., Cosimi, A. B., & Kawai, T. (2012). Overcoming memory T-cell responses for induction of delayed tolerance in nonhuman primates. American Journal of Transplantation, 12, 330–340.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  • Gerald Brandacher
    • 1
  • Maria Chicco
    • 1
  • W. P. Andrew Lee
    • 1
  1. 1.Department of Plastic and Reconstructive SurgeryVascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of MedicineBaltimoreUSA

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