Large Animal Models for Vascularized Composite Allotransplantation

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Vascularized composite allograft transplant survival in miniature swine: is MHC tolerance sufficient for acceptance of epidermis? Transplantation. 2013;96(11):966–74. Using a model of established MHC tolerance the authors show that MHC tolerance alone is not sufficient for tolerance of skin. Fuchimoto Y, Huang CA, Yamada K, Shimizu A, Kitamura H, Colvin RB, et al. Mixed chimerism and tolerance without whole body irradiation in a large animal model. J Clin Invest. 2000;105(12):1779–89. Kuo YR, Chen CC, Shih HS, Goto S, Huang CW, Wang CT, et al. Mesenchymal stem cells prolong composite tissue allotransplant survival in a swine model. Transplantation. 2009;87(12):1769–77. Kuo YR, Chen CC, Shih HS, Goto S, Huang CW, Wang CT, et al. Prolongation of composite tissue allotransplant survival by treatment with bone marrow mesenchymal stem cells is correlated with T-cell regulation in a swine hind-limb model. Plast Reconstr Surg. 2011;127(2):569–79. Kuo YR, Chen CC, Goto S, Huang YT, Wang CT, Tsai CC, et al. Immunomodulatory effects of bone marrow-derived mesenchymal stem cells in a swine hemi-facial allotransplantation model. PLoS One. 2012;7(4):e35459. Leonard DA, Kurtz JM, Mallard C, Albritton A, Duran-Struuck R, Farkash EA, et al. Vascularized Composite Allograft Tolerance Across MHC Barriers in a Large Animal Model. Am J Transplant. 2014;14:343–55. Using a non-myeloblative conditioning with BMT the authors transplant a myocutaneous flap in a haplotype mismatch animal with tolerance to all components of the graft. This is associated with chimerism and GVHD. Goldwyn RM, Beach PM, Feldman D, Wilson RE. Canine limb homotransplantations. Plast Reconstr Surg. 1966;37:184–95. Lance EM, Inglis AE, Figarola F. Transplantation of the canine hind limb. Surgical technique and methods of immunosuppression for allotransplantation. A preliminary report. J Bone Joint Surg Am. 1971;53:1137–49. Shengwu Z, Qingfeng L, Hao J, Banich J, Kaiding F, Benson C, et al. Developing a canine model of composite facial/scalp allograft transplantation. Ann Plast Surg. 2007;59(2):185–94. Eduardo Bermú Dez L, Santamaría A, Romero T, Calderó DF. Experimental model of facial transplant. Plast Reconstr Surg. 2002;110:1374–5. Mathes DW, Noland M, Graves S, Schlenker R, Miwongtum T, Storb R. A preclinical canine model for composite tissue transplantation. J Reconstr Microsurg. 2010;26(3):201–7. Mathes DW, Huang B, Graves SS, Edwards J, Chang J, Storer BE, et al. Tolerance to vascularized composite allografts in canine mixed hematopoietic chimeras. Transplantation. 2011;92:1301–8. This study demonstrates that a nonmyeloablative hematopoeitic stem cell transplant conditioning regimen is an effective means of establishing stable, mixed chimerism with subsequent evidence of donor-specific tolerance. Further, T-regulatory cells may participate in maintenance of the vascularized composite allograft.