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.
Keywords
- Vascularized Composite Allotransplantation (VCA)
- Composite Tissue Allotransplantation (CTA)
- Uterine Transplantation
- Face Transplantation
- Mixed Chimerism
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.
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References
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.
Balayla, J. (2016). Uterine transplants in the Canadian setting: A theoretical framework. Journal of Obstetrics and Gynaecology Canada, 38, 955–960.
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.
Billingham, R. E., Brent, L., & Medawar, P. B. (1953). Activity acquired tolerance of foreign cells. Nature, 172, 603–606.
Brandacher, G., Lee, W. P., & Schneeberger, S. (2012). Minimizing immunosuppression in hand transplantation. Expert Review of Clinical Immunology, 8, 673–683.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Diefenbeck, M., Nerlich, A., Schneeberger, S., Wagner, F., & Hofmann, G. O. (2011). Allograft vasculopathy after allogeneic vascularized knee transplantation. Transplant International, 24, 1–5.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Gilbert, R. (1964). Hand transplanted from a cadaver is reamputated. Medical Tribune and Medical News, 5, 23.
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.
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.
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.
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.
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.
Jones, N. F. (2002). Concerns about human hand transplantation in the 21st century. The Journal of Hand Surgery, 27, 771–787.
Jones, N. F., & Schneeberger, S. (2009). Arm transplantation: Prospects and visions. Transplantation Proceedings, 41, 476–480.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Levitsky, J. (2011). Operational tolerance: Past lessons and future prospects. Liver Transplantation, 17, 222–232.
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.
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.
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.
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.
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.
Morelon, E., Kanitakis, J., & Petruzzo, P. (2012). Immunological issues in clinical composite tissue allotransplantation: Where do we stand today? Transplantation, 93, 855–859.
Morelon, E., Kanitakis, J., Petruzzo, P., Badet, L., & Thaunat, O. (2015). Immunological challenges in vascularised composite allotransplantation. Current Transplantation Reports, 2, 276–283.
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.
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.
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.
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.
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.
Petruzzo, P., & Dubernard, J. M. (2011). The international registry on hand and composite tissue allotransplantation. Clinical Transplants, 247–253.
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.
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.
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.
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.
Ravindra, K. V., & Ildstad, S. T. (2011). Immunosuppressive protocols and immunological challenges related to hand transplantation. Hand Clinics, 27, 467–479.
Rudensky, A. Y. (2011). Regulatory T cells and Foxp3. Immunological Reviews, 241, 260–268.
Sachs, D. H., Kawai, T., & Sykes, M. (2014). Induction of tolerance through mixed chimerism. Cold Spring Harbor Perspectives in Medicine, 4, 1–19.
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.
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.
Scheib, J., & Höke, A. (2013). Advances in peripheral nerve regeneration. Nature Reviews. Neurology, 9, 668–676.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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Brandacher, G., Chicco, M., Andrew Lee, W.P. (2017). New Strategies in Composite Tissue Allotransplantation. In: Nadig, S., Wertheim, J. (eds) Technological Advances in Organ Transplantation. Springer, Cham. https://doi.org/10.1007/978-3-319-62142-5_9
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