A heterotopic primate model for facial composite tissue transplantation.

University of Maryland School of Medicine, Department of Surgery, Baltimore, MD 21201, USA.
Annals of Plastic Surgery (Impact Factor: 1.38). 03/2008; 60(2):209-16. DOI: 10.1097/SAP.0b013e318061b792
Source: PubMed

ABSTRACT The purpose of this study was to develop a nonhuman primate model for heterotopic composite tissue facial transplantation in which to study the natural history of facial transplantation and evaluate immunosuppressive regimens.A composite oromandibular facial segment transplant based on the common carotid artery was evaluated. Flaps from 7 cynomolgus monkeys were transplanted to the groins of 7 recipients at the superficial femoral artery and vein. The immunosuppressive regimen consisted of thymoglobulin, rapamycin, and tacrolimus. Allograft survival ranged from 6 to 129 days. Histology performed in the long-term survivor at the time of necropsy revealed extensive inflammation and necrosis of the allograft skin; however, muscle and bone elements were viable, with minimal inflammation. This heterotopic facial transplantation model avoids the potential morbidity of mandibular resection and orthotopic facial transplantation. Our work also concurs with the work of other groups who found that the skin component is the most antigenic.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Vascularized composite tissue allotransplantation is a viable treatment option for injuries and defects that involve multiple layers of functional tissue. In the past 15 yr, more than 150 vascularized composite allotransplantation (VCA) surgeries have been reported for various anatomic locations including - but not limited to - trachea, larynx, abdominal wall, face, and upper and lower extremities. VCA can achieve a level of esthetic and functional restoration that is currently unattainable using conventional reconstructive techniques. Although the risks of lifelong immunosuppression continue to be an important factor when evaluating the benefits of VCA, reported short- and long-term outcomes have been excellent, thus far. Acute rejections are common in the early post-operative period, and immunosuppression-related side effects have been manageable. A multidisciplinary approach to the management of VCA has proven successful. Reports of long-term graft losses have been rare, while several factors may play a role in the pathophysiology of chronic graft deterioration in VCA. Alternative approaches to immunosuppression such as cellular therapies and immunomodulation hold promise, although their role is so far not defined. Experimental protocols for VCA are currently being explored. Moving forward, it will be exciting to see whether VCA-specific aspects of allorecognition and immune responses will be able to help facilitate tolerance induction.
    Clinical Transplantation 04/2013; · 1.63 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The preclinical experimental models of vascularized composite allografts (VCAs) have been rapidly developed for the assessment of immunomodulatory protocols for clinical application. Recently, researchers have focused on immunomodulatory protocols which overcome the immunologic barrier between the allogeneic donor and recipient and may lead to tolerance induction. In order to test the feasibility of chimerism induction, experimental VCAs have been performed in different models including rodents, large animals, and nonhuman primates. These models differ in the complexity of transplanted tissue and in their responses to immunomodulatory protocols. In most applications, VCA contains multiple-tissue components; however, each individual component of CTA possesses unique immunologic characteristics that ultimately contribute to the chimerism induction and successful outcome of the VCA. Heterogenic character and complexity of tissue components in different VCA models determine the quality and robustness of donor-specific chimerism. As introduced in experimental studies, variable immunomodulatory options have been studied to achieve tolerance to VCA in rodents and large animal models allowing for widespread application in clinic. In this paper, based on our own experience, we have analyzed the current knowledge of tolerance-inducing strategies via chimerism induction in VCA experimental models in the context of immunomodulatory protocols and VCA complexity and their relevance and applicability to clinical practice.
    Clinical and Developmental Immunology 01/2013; 2013:831410. · 3.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Currently, only a few large animal models, including swine, dog, and nonhuman primate, are described for composite face transplantation studies and the literature lacks reports on the large animal model of composite auricular transplantation. Large animal models offer better understanding of the immunological mechanisms and major histocompatibility complex characterization and, for this reason, are preferred to the small animal models for the assessment of new immunosuppressive tolerance induction protocols. Thus, the aim of this study was to demonstrate feasibility of dissection and exploration of vascular territories of the hemifacial and auricle transplantation models in the sheep cadavers. Ten cadaver sheep heads were studied. The vascular territories of the composite hemifacial flap and composite auricle flap were defined by anatomical dissection. Methylene blue staining and laser-assisted indocyanine green angiography using SPY Elite System were used for vascular territories assessment. The dissection of cadaver sheep heads confirmed that the hemifacial flap and auricle flap can be raised on the same pedicle consisting of the common carotid artery and jugular vein. An adequate vascular network was observed in the flaps after injection of methylene blue dye via the arterial pedicle. Laser-assisted indocyanine green angiography identified vascular territories of the hemifacial and auricular vascular network. We described a new hemifacial and an auricular transplantation models in the sheep cadavers and have confirmed presence of the adequate vascular network as demonstrated by the laser-assisted angiography. This study introduces 2 new large animal models into the armamentarium of vascular composite allotransplantation.
    Annals of plastic surgery 04/2014; 72(4):469-74. · 1.29 Impact Factor