Subscribe to RSS
DOI: 10.1055/s-0030-1247717
A Preclinical Canine Model for Composite Tissue Transplantation
Publication History
Publication Date:
27 January 2010 (online)
ABSTRACT
The feasibility of composite tissue allografts (CTAs) has been demonstrated by the successful transplantation of the hand, abdomen, and face. However, the survival of these transplants depends on immunosuppression. Our laboratory is interested in achieving tolerance to decrease the risks associated with the use of chronic immunosuppression. The purpose of this experiment was to develop a large-animal model for CTA. Four canine flaps were autotransplanted to examine the use of a myocutaneous rectus flap based on the deep inferior epigastric vessels. Five CTA transplants were performed between dog leukocyte antigen (DLA)-identical littermates without posttransplant immunosuppression. The allografts were followed clinically and underwent routine biopsies. The anatomic dissections and autotransplants were all successful and revealed that the flap could be divided into two separate components. Skin was perfused by the superficial epigastric artery. Rectus muscle was perfused by the deep inferior epigastric system. This allowed the allografts to be transplanted as muscle or skin or with both components based on the external iliac artery and veins. The DLA-identical littermates rejected the allografts in 15 to 30 days. This study demonstrated the versatility of the myocutaneous rectus flap for use in canines as CTA models.
KEYWORDS
Composite tissue allograft - large-animal model - skin rejection - muscle rejection - canine
REFERENCES
- 1 Siemionow M, Nasir S. Chimerism and bone marrow based therapies in transplantation. Microsurgery. 2007; 27 510-521
- 2 International Registry on Hand and Composite Tissue Transplantation .Available at: http://www.handregistry.com/page.asp?page=4 Accessed August 1, 2009
- 3 Lanzetta M, Petruzzo P, Dubernard J M et al.. Second report (1998–2006) of the International Registry of Hand and Composite Tissue Transplantation. Transpl Immunol. 2007; 18 1-6
- 4 Whitaker I S, Duggan E M, Alloway R R et al.. Composite tissue allotransplantation: a review of relevant immunological issues for plastic surgeons. J Plastic Reconstr Aesthet Surg. 2008; 61 481-492
- 5 Mihatsch M J, Kyo M, Morozumi K, Yamaguchi Y, Nickeleit V, Ryffel B. The side-effects of ciclosporine-A and tacrolimus. Clin Nephrol. 1998; 49 356-363
- 6 Philip A T, Gerson B. Toxicology and adverse effects of drugs used for immunosuppression in organ transplantation. Clin Lab Med. 1998; 18 755-765
- 7 Mele T S, Halloran P F. The use of mycophenolate mofetil in transplant recipients. Immunopharmacology. 2000; 47 215-245
- 8 Fardet L, Kassar A, Cabane J, Flahault A. Corticosteroid-induced adverse events in adults: frequency, screening and prevention. Drug Saf. 2007; 30 861-881
- 9 Fishman J A, Rubin R H. Infection in organ-transplant recipients. N Engl J Med. 1998; 338 1741-1751
- 10 Schneeberger S, Lucchina S, Lanzetta M et al.. Cytomegalovirus-related complications in human hand transplantation. Transplantation. 2005; 80 441-447
- 11 Baumeister S, Kleist C, Döhler B, Bickert B, Germann G, Opelz G. Risks of allogeneic hand transplantation. Microsurgery. 2004; 24 98-103
- 12 Storb R, Yu C, Wagner J L et al.. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood. 1997; 89 3048-3054
- 13 Yu C, Seidel K, Nash R A et al.. Synergism between mycophenolate mofetil and cyclosporine in preventing graft-versus-host disease among lethally irradiated dogs given DLA-nonidentical unrelated marrow grafts. Blood. 1998; 91 2581-2587
- 14 Yu C, Storb R, Mathey B et al.. DLA-identical bone marrow grafts after low-dose total body irradiation: effects of high-dose corticosteroids and cyclosporine on engraftment. Blood. 1995; 86 4376-4381
- 15 Storb R, Raff R F, Appelbaum F R et al.. FK-506 and methotrexate prevent graft-versus-host disease in dogs given 9.2 Gy total body irradiation and marrow grafts from unrelated dog leukocyte antigen-nonidentical donors. Transplantation. 1993; 56 800-807
- 16 Storb R, Epstein R B, Rudolph R H, Thomas E D. Allogeneic canine bone marrow transplantation following cyclophosphamide. Transplantation. 1969; 7 378-386
- 17 Storb R, Epstein R B, Graham T C, Thomas E D. Methotrexate regimens for control of graft-versus-host disease in dogs with allogeneic marrow grafts. Transplantation. 1970; 9 240-246
- 18 Wagner J L, Burnett R C, DeRose S A, Francisco L V, Storb R, Ostrander E A. Histocompatibility testing of dog families with highly polymorphic microsatellite markers. Transplantation. 1996; 62 876-877
- 19 Wagner J L, Works J D, Storb R. DLA-DRB1 and DLA-DQB1 histocompatibility typing by PCR-SSCP and sequencing. Tissue Antigens. 1998; 52 397-401
- 20 World's first face and double-hand transplant patient dies in France. The Daily Telegraph June 16, 2009. Available at: http://www.dailytelegraph.com.au/news/world/worlds-first-face-and-and-double-hand-transplant-patient-dies-in-france/story-e6frev00-1225736077918 Accessed August 15, 2009
- 21 Kirk A D. Crossing the bridge: large animal models in translational transplantation research. Immunol Rev. 2003; 196 176-196
- 22 Ikeguchi R, Sacks J M, Unadkat J V et al.. Long-term survival of limb allografts induced by pharmacologically conditioned, donor alloantigen-pulsed dendritic cells without maintenance immunosuppression. Transplantation. 2008; 85 237-246
- 23 Demir Y, Ozmen S, Klimczak A, Mukherjee A L, Siemionow M. Tolerance induction in composite facial allograft transplantation in the rat model. Plast Reconstr Surg. 2004; 114 1790-1801
- 24 Blattman J N, Antia R, Sourdive D J et al.. Estimating the precursor frequency of naive antigen-specific CD8 T cells. J Exp Med. 2002; 195 657-664
- 25 Siemionow M, Unal S. Strategies for tolerance induction in nonhuman primates. Ann Plast Surg. 2005; 55 545-553
- 26 Cendales L C, Xu H, Bacher J, Eckhaus M A, Kleiner D E, Kirk A D. Composite tissue allotransplantation: development of a preclinical model in nonhuman primates. Transplantation. 2005; 80 1447-1454
- 27 Goldwyn R M, Beach P M, Feldman D, Wilson R E. Canine limb homotransplantation. Plast Reconstr Surg. 1966; 37 184-195
- 28 Wagner J L, Burnett R C, Storb R. Organization of the canine major histocompatibility complex: current perspectives. J Hered. 1999; 90 35-38
- 29 Ochiai T, Nagata M, Nakajima K et al.. Studies of the effects of FK506 on renal allografting in the beagle dog. Transplantation. 1987; 44 729-733
- 30 Storb R, Yu C, Wagner J L et al.. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood. 1997; 89 3048-3054
- 31 Yu C, Seidel K, Nash R A et al.. Synergism between mycophenolate mofetil and cyclosporine in preventing graft-versus-host disease among lethally irradiated dogs given DLA-nonidentical unrelated marrow grafts. Blood. 1998; 91 2581-2587
- 32 Storb R, Raff R F, Appelbaum F R et al.. FK-506 and methotrexate prevent graft-versus-host disease in dogs given 9.2 Gy total body irradiation and marrow grafts from unrelated dog leukocyte antigen-nonidentical donors. Transplantation. 1993; 56 800-807
- 33 Luznik L, O'Donnell P V, Symons H J et al.. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008; 14 641-650
- 34 Maris M B, Niederwieser D, Sandmaier B M et al.. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood. 2003; 102 2021-2030
David W MathesM.D.
Assistant Professor of Surgery, University of Washington
Department of Surgery, Box 356410, Seattle, WA 98195
Email: dwmathes@u.washington.edu