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Experimental Approaches to Composite Tissue Allograft Transplants

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Hand Transplantation

Abstract

Composite tissue allotransplantation has been recently introduced as a potential clinical treatment for complex reconstructive procedures, include traumatic injuries, cancer ablative surgeries, or extensive tissue loss secondary to burns. Composite tissue allografts (CTAs) consist of heterogeneous tissues derived from ectoderm and mesoderm, including skin, fat, muscle, nerves, lymph nodes, bone, cartilage, ligaments, and bone marrow, with different antigenicity. Thus, composite tissue structure is considered to be more immunogenic than solid organ transplants. While cartilage, ligaments, and fat present low antigenicity, bone, muscles, nerves, and vessels present moderate antigenicity, and skin is the component that develops the most severe rejection because of the abundance of dendritic cells within the epidermis and dermis. To study the mechanisms of CTA acceptance and rejection, different experimental models, strategies and different immunosuppressive protocols have used [1, 2].

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References

  1. Lee WP, Yaremchuk MJ, Pan YC et al (1991) Relative antigenicity of components of a vascularized limb allograft. Plast Reconstr Surg 87(3):401–411

    Article  PubMed  CAS  Google Scholar 

  2. Cendales LC, Xu H, Bacher J et al (2005) Composite tissue allotransplantation: development of a preclinical model in nonhuman primates. Transplantation 80(10):1447–1454

    Article  PubMed  Google Scholar 

  3. Lance EM, Inglis AE, Figarola F et al (1971) Transplantation of the canine hind limb. Surgical technique and methods of immunosuppression for allotransplantation. A preliminary report. J Bone Joint Surg Am 53(6):1137–1149

    PubMed  CAS  Google Scholar 

  4. Jensen JN, Mackinnon SE (2000) Composite tissue allotransplantation: a comprehensive review of the literature — part 1. J Reconstr Microsurg 16(1):57–68

    PubMed  CAS  Google Scholar 

  5. Shapiro RI, Cerra FB (1978) A model for reimplantation and transplantation of a complex organ: the rat hind limb. J Surg Res 24(6):501–506

    Article  PubMed  CAS  Google Scholar 

  6. Palm J, Black G (1971) Interrelationships of inbred rat strains with respect to Ag-B and non-Ag-B antigens. Transplantation 11(2):184–189

    Article  PubMed  CAS  Google Scholar 

  7. Gill TJ (1978) Report of the first international workshop on alloantigenic systems in the rat. Transplant Proc X:271

    Google Scholar 

  8. Doi K (1979) Homotransplantation of limbs in rats. A preliminary report on an experimental study with nonspecific immunosuppressive drugs. Plast Reconstr Surg 64(5):613–621

    Article  PubMed  CAS  Google Scholar 

  9. Black KS, Hewitt CW, Fraser LA et al (1982) Cosmas and Damian in the laboratory. N Engl J Med 306(6):368–369

    Article  PubMed  CAS  Google Scholar 

  10. Black KS, Hewitt CW, Fraser LA et al (1985) Composite tissue (limb) allografts in rats. II. Indefinite survival using low-dose cyclosporine. Transplantation 39(4):365–368

    Article  PubMed  CAS  Google Scholar 

  11. Hewitt CW, Black KS, Fraser LA et al (1985) Composite tissue (limb) allografts in rats. I. Dose-dependent increase in survival with cyclosporine. Transplantation 39(4):360–364

    Article  PubMed  CAS  Google Scholar 

  12. Press BH, Sibley RK, Shons AR (1986) Limb allotransplantation in the rat: extended survival and return of nerve function with continuous cyclosporin/prednisone immunosuppression. Ann Plast Surg 16(4):313–321

    Article  PubMed  CAS  Google Scholar 

  13. Inceoglu S, Siemionow M, Chick L et al (1994) The effect of combined immunosuppression with systemic low-dose cyclosporin and topical fluocinolone acetonide on the survival of rat hind-limb allografts. Ann Plast Surg 33(1):57–65

    Article  PubMed  CAS  Google Scholar 

  14. Arai K, Hotokebuchi T, Miyahara H et al (1989) Limb allografts in rats immunosuppressed with FK506. I. Reversal of rejection and indefinite survival. Transplantation 48(5):782–786

    Article  PubMed  CAS  Google Scholar 

  15. Buttemeyer R, Jones NF, Min Z et al (1996) Rejection of the component tissues of limb allografts in rats immunosuppressed with FK-506 and cyclosporine. Plast Reconstr Surg 97(1):139–148; discussion 149–151

    Article  PubMed  CAS  Google Scholar 

  16. Benhaim P, Anthony JP, Ferreira L et al (1996) Use of combination of low-dose cyclosporine and RS-61443 in a rat hindlimb model of composite tissue allotransplantation. Transplantation 61(4):527–532

    Article  PubMed  CAS  Google Scholar 

  17. Muramatsu K, Doi K, Kawai S (1999) Limb allotransplantation in rats: combined immunosuppression by FK-506 and 15-deoxyspergualin. J Hand Surg [Am] 24(3):586–593

    Article  CAS  Google Scholar 

  18. Ustuner ET, Zdichavsky M, Ren X et al (1998) Long-term composite tissue allograft survival in a porcine model with cyclosporine/mycophenolate mofetil therapy. Transplantation 66(12):1581–1587

    Article  PubMed  CAS  Google Scholar 

  19. Jones JW Jr, Ustuner ET, Zdichavsky M et al (1999) Long-term survival of an extremity composite tissue allograft with FK506-mycophenolate mofetil therapy. Surgery 126(2):384–388

    Article  PubMed  Google Scholar 

  20. Lee WP, Rubin JP, Cober S et al (1998) Use of swine model in transplantation of vascularized skeletal tissue allografts. Transplant Proc 30(6):2743–2745

    Article  PubMed  CAS  Google Scholar 

  21. Daniel RK, Egerszegi EP, Samulack DD et al (1986) Tissue transplants in primates for upper extremity reconstruction: a preliminary report. J Hand Surg [Am] 11:1–8

    CAS  Google Scholar 

  22. Stark GB, Swartz WM, Narayanan K et al (1987) Hand transplantation in baboons. Transplant Proc 19:3968–3971

    PubMed  CAS  Google Scholar 

  23. Stevens HPJD, Hovius SER, Vuzevski VD et al (1990) Immunolojical aspects of allogeneic partial hand transplantation in the rhesus monkey. Transplant Proc 22:2006–2008

    PubMed  CAS  Google Scholar 

  24. Gold ME, Randzio J, Kniha H et al (1991) Transplantation of vascularized composite mandibular allografts in young cynomolgus monkeys. Ann Plast Surg 26:125–132

    Article  PubMed  CAS  Google Scholar 

  25. Mjornstedt L, Olausson M, Lindholm L et al (1987) Mechanisms maintaining transplantation tolerance in antithymocyte globulin-treated rats. Transplantation 44(5):669–673

    Article  PubMed  CAS  Google Scholar 

  26. Gammie JS, Li S, Colson YL et al (1998) A partial conditioning strategy for achieving mixed chimerism in the rat: tacrolimus and anti-lymphocyte serum substantially reduce the minimum radiation dose for engraftment. Exp Hematol 26(10):927–935

    PubMed  CAS  Google Scholar 

  27. Wood ML, Monaco AP, Gozzo JJ et al (1971) Use of homozygous allogeneic bone marrow for induction of tolerance with antilymphocyte serum: dose and timing. Transplant Proc 3(1):676–679

    PubMed  CAS  Google Scholar 

  28. Siemionow M, Oke R, Ozer K et al (2002) Induction of donor-specific tolerance in rat hind-limb allografts under antilymphocyte serum and cyclosporine A protocol. J Hand Surg [Am] 27(6):1095–1103

    Article  Google Scholar 

  29. Ozer K, Gurunluoglu R, Zielinski M et al (2003) Extension of composite tissue allograft survival across major histocompatibility barrier under short course of anti-lymphocyte serum and cyclosporine a therapy. J Reconstr Microsurg 19(4):249–256

    Article  PubMed  Google Scholar 

  30. Heidecke CD, Hancock WW, Jakobs F et al (1995) Alpha/beta-T cell receptor-directed therapy in rat cardiac allograft recipients. Treatment prior to alloantigen exposure prevents sensitization and abrogates accelerated rejection. Transplantation 59(1):78–84

    Article  PubMed  CAS  Google Scholar 

  31. Siemionow M, Cunningham B, Ortak T (2000) A new model for induction of tolerance in composite tissue allografts combined limb-thymus transplantation. J Hand Surg [Br] 25[Suppl. 1]:50

    Google Scholar 

  32. Siemionow M, Ortak T, Izycki D (2002) Induction of tolerance in composite-tissue allografts. Transplantation 74(9):1211–1217

    Article  PubMed  CAS  Google Scholar 

  33. Ozer K, Izycki D, Zielinski M et al (2004) Development of donor-specific chimerism and tolerance in composite tissue allografts under alphabeta-T-cell receptor monoclonal antibody and cyclosporine a treatment protocols. Microsurgery 24(3):248–254

    Article  PubMed  Google Scholar 

  34. Siemionow MZ, Izycki DM, Zielinski M (2003) Donorspecific tolerance in fully major histocompatibility major histocompatibility complex-mismatched limb allograft transplants under an anti-alphabeta T-cell receptor monoclonal antibody and cyclosporine A protocol. Transplantation 27;76(12):1662–1668

    Article  PubMed  CAS  Google Scholar 

  35. Ozer K, Oke R, Gurunluoglu R et al (2003) Induction of tolerance to hind limb allografts in rats receiving cyclosporine A and antilymphocyte serum: effect of duration of the treatment. Transplantation 75(1):31–36

    Article  PubMed  CAS  Google Scholar 

  36. Siemionow M, Izycki D, Ozer K et al (2006) Role of thymus in operational tolerance induction in limb allograft transplant model. Transplantation 81(11):1568–1576

    Article  PubMed  Google Scholar 

  37. Siemionow M, Ulusal BG, Ozmen S et al (2004) Composite vascularized skin/bone graft model: a viable source for vascularized bone marrow transplantation. Microsurgery 24(3):200–206

    Article  PubMed  Google Scholar 

  38. Ozmen S, Ulusal BG, Ulusal AE et al (2006) Composite vascularized skin/bone transplantation models for bone marrow-based tolerance studies. Ann Plast Surg 56(3):295–300

    Article  PubMed  CAS  Google Scholar 

  39. Siemionow M, Ozer K, Izycki D et al (2005) A new method of bone marrow transplantation leads to extension of skin allograft survival. Transplant Proc 37(5):2309–2314

    Article  PubMed  CAS  Google Scholar 

  40. Siemionow MZ, Klimczak A, Unal S (2005) Different routes of donor-derived hematopoietic stem cell transplantation for donor-specific chimerism induction across MHC barrier. Transplant Proc 37(1):62–64

    Article  PubMed  CAS  Google Scholar 

  41. Demir Y, Ozmen S, Klimczak A et al (2005) Strategies to develop chimerism in vascularized skin allografts across MHC barrier. Microsurgery 25(5):415–422

    Article  PubMed  Google Scholar 

  42. Hewitt CW, Ramsamooj R, Patel MP et al (1990) Development of stable mixed T cell chimerism and transplantation tolerance without immune modulation in recipients of vascularized bone marrow allografts. Transplantation 50(5):766–772

    Article  PubMed  CAS  Google Scholar 

  43. Lukomska B, Durlik M, Pienkowska B et al (1990) Transplantation of bone marrow with vascularized bone. Transplant Proc 22(5):2255–2256

    PubMed  CAS  Google Scholar 

  44. Suzuki H, Patel N, Matthews M et al (2000) Vascularized bone marrow transplantation: A new surgical approach using isolated femoral bone/bone marrow. J Surg Res 89(2):176–183

    Article  PubMed  CAS  Google Scholar 

  45. Santiago SF, de Faria W, Khan TF et al (1999) Heterotopic sternum transplant in rats: a new model of a vascularized bone marrow transplantation. Microsurgery 19(7):330–334

    Article  PubMed  CAS  Google Scholar 

  46. Muramatsu K, Valenzuela RG, Bishop AT (2003) Detection of chimerism following vascularized bone allotransplantation by polymerase chain reaction using a Y-chromosome specific primer. J Orthop Res 21(6):1056–1062

    Article  PubMed  CAS  Google Scholar 

  47. Siemionow M, Ozer K (2002) Advances in composite tissue allograft transplantation as related to the hand and upper extremity. J Hand Surg [Am] 27(4):565–580

    Article  Google Scholar 

  48. Siemionow M, Klimczak A, Unal S (2004) Different routes of donor derived hematopoietic stem cells transplantation for donor specific chimerism induction across MHC barrier. XX International Congress of The Transplantation Society, Vienna

    Google Scholar 

  49. Tai CY, France MA, Strande LF et al (2003) An extraperitoneal isolated vascularized bone marrow transplant model in the rat. Transplantation 75:1591

    Article  PubMed  Google Scholar 

  50. Agaoglu G, Unal S, Siemionow M (2005). Transplantation of the vascularized bone allograft into the inguinal region. Plast Reconstr Surg 115(6):1794–1795

    Article  PubMed  CAS  Google Scholar 

  51. Agaoglu G, Carnevale KA, Zins JE Siemionow M (2006). Bilateral vascularized femoral bone transplant: a new model of vascularized bone marrow transplantation in rats, part I. Ann Plast Surg 56(6):658–664

    Article  PubMed  CAS  Google Scholar 

  52. Klimczak A, Agaoglu G, Carnevale KA, Siemionow M (2006) Applications of bilateral vascularized femoral bone marrow transplantation for chimerism induction. Ann Plast Surg [In press]

    Google Scholar 

  53. Yazici I, Unal S, Siemionow M (2005) Composite hemiface/calvarium transplantation model in rat. Plast Reconst Surg [In press]

    Google Scholar 

  54. Yazici I, Carnevale Kevin, Klimczak A, Siemionow M (2006) A new rat model of maxilla allotransplantation. Ann Plast Surg [In press]

    Google Scholar 

  55. Kulahci Y, Molski M, Siemionow M (2006) Development of the alternative composite tissue allograft transplantation models for reconstruction of the head and neck defects. 51st Annual Meeting of the Plastic Surgery Research Council. May 17–20, Dana Point, California

    Google Scholar 

  56. Kulahci Y, Klimczak A, Siemionow M (2006) Development and maintenance of donor specific chimerism in semi-allogeneic major histocompatibility complex mismatched hemiface/mandible/tongue flap under low dose cyclosporine a treatment. The combined Meeting of the Ohio Valley and the Robert H. Ivy Societies of Plastic Surgeons. June 2–4, Pittsburgh, Pennsylvania

    Google Scholar 

  57. Agaoglu G, Siemionow M (2005) Combined semimem-branosus muscle and epigastric skin flap: a new model of composite-free flap in the rat. Ann Plast Surg 55(3):310–315

    Article  PubMed  CAS  Google Scholar 

  58. Ozer K, Zielinski M, Siemionow M (2003) New composite tissue allograft transplantation model in mouse with intravital microscopic evaluation of microcirculation. J Reconstr Microsurg 19(5):323–330

    Article  PubMed  Google Scholar 

  59. Strome S, Sloman-Moll E, Samonte BR et al (1992) Rat model for a vascularized laryngeal allograft. Ann Otol Rhinol Laryngol 101(11):950–953

    PubMed  CAS  Google Scholar 

  60. Lorenz RR, Dan O, Fritz MA et al (2002) Rat laryngeal transplant model: technical advancements and a redefined rejection grading system. Ann Otol Rhinol Laryngol 111(12 Pt 1):1120–1127

    PubMed  Google Scholar 

  61. Akst LM, Siemionow M, Dan O et al (2003) Induction of tolerance in a rat model of laryngeal transplantation. Transplantation 76(12):1763–1770

    Article  PubMed  CAS  Google Scholar 

  62. Siemionow M, Gozel-Ulusal B, Engin Ulusal A et al (2003) Functional tolerance following face transplantation in the rat. Transplantation 75(9):1607–1609

    Article  PubMed  Google Scholar 

  63. Ulusal BG, Ulusal AE, Ozmen S et al (2003) A new composite facial and scalp transplantation model in rats. Plast Reconstr Surg 112(5):1302–1311

    Article  PubMed  Google Scholar 

  64. Unal S, Agaoglu G, Zins J et al (2005) New surgical approach in facial transplantation extends survival of allograft recipients. Ann Plast Surg 55(3):297–303

    Article  PubMed  CAS  Google Scholar 

  65. Demir Y, Ozmen S, Klimczak A et al (2004) Tolerance induction in composite facial allograft transplantation in the rat model. Plast Reconstr Surg 114(7):1790–801

    Article  PubMed  Google Scholar 

  66. Demir Y, Ozmen S, Klimczak A et al (2006) The efficacy of different immunosuppressive treatment protocols on survival and development of chimerism in vascularized skin allograft transplants across MHC barrier. Plast Reconstr Surg [In press]

    Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Plastic Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio, USA

    Maria Siemionow & Yalcin Kulahci

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  1. Maria Siemionow
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  2. Yalcin Kulahci
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Editor information

Editors and Affiliations

  1. Italian Institute of Hand Surgery, Monza,Milan, Italy

    Marco Lanzetta (Director, Adjunct Professor and President) (Director, Adjunct Professor and President)

  2. University of Canberra, Australia

    Marco Lanzetta (Director, Adjunct Professor and President) (Director, Adjunct Professor and President)

  3. International Hand and Composite, Tissue Allograft Society, Australia

    Marco Lanzetta (Director, Adjunct Professor and President) (Director, Adjunct Professor and President)

  4. Department of Transplantation, Édouard Herriot Hospital, Lyon, France

    Jean-Michel Dubernard  & Palmina Petruzzo  & 

  5. Department of Surgery, University of Cagliari, Italy

    Palmina Petruzzo

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© 2007 Springer-Verlag Italia

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Siemionow, M., Kulahci, Y. (2007). Experimental Approaches to Composite Tissue Allograft Transplants. In: Lanzetta, M., Dubernard, JM., Petruzzo, P. (eds) Hand Transplantation. Springer, Milano. https://doi.org/10.1007/978-88-470-0374-3_7

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  • DOI: https://doi.org/10.1007/978-88-470-0374-3_7

  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-0373-6

  • Online ISBN: 978-88-470-0374-3

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