All animals exhibited indefinite survival of the musculoskeletal portion of their allografts but only prolonged survival of the epidermis. The loss of the graft skin appears to be the result of an isolated immune reaction to the skin, and, in particular, the epidermis. This observation is further substantiated by the accelerated rejection of secondarily placed frozen donor skin grafts.
The purpose of this article is to review the historical background and clinical status of composite tissue allotransplantation and to discuss the scientific evolution of clinical face transplantation. Composite tissue allotransplantation (CTA) rapidly progressed in the 1980s with the discovery of cyclosporine. Although the most success has been achieved with hand transplantation, others have made progress with allografts of trachea, peripheral nerve, flexor tendon apparatus, vascularized knee, larynx, abdominal wall, and most recently, partial face. The world's first partial face allotransplantation occurred in November 2005 in France. In April of 2006, there was a second performed in China. As of today, there are now multiple institutions with plans to attempt the world's first full facial/scalp transplant. Complete facial/scalp allotransplantation offers a viable alternative for unfortunate individuals suffering severe facial disfigurement and is a product of many decades of experimental research, beginning with rat hindlimb allografts.
Neural stem cells show a remarkable aptitude for integration and appropriate differentiation at sites of cellular injury in central nervous system (CNS) disease models. In contrast, reports of neural stem cell applications in peripheral nerve injury models are sparse. In this study we sought to determine if the C17.2 cell line would respond to cues in the microenvironment of the injured peripheral nerve and enhance neuronal regeneration in rodent sciatic nerve injury models. We transplanted C17.2 into several sciatic nerve injury models in 45 nude rats, including nerve transection, nerve crush, and nerve gap models. Twelve of the animals in this study developed large tumors at the site of neural stem cell transplants. Histologically, the tumors resembled neuroblastomas. The tumors were confirmed to be of transplanted cell origin by positive beta-galactosidase staining. Tumors occurred only in models where the nerve remained intact or where continuity of the nerve was restored. We concluded that C17.2 transplantation into peripheral nerve injury models resulted in a high rate of tumor formation. This study demonstrates that the success of neural precursor transplants in the CNS cannot necessarily be extrapolated to the peripheral nervous system.
Current rodent models for investigation of limb allotransplantation typically utilize orthotopic whole-limb transplantation, a morbid and time-consuming procedure. Our objective was to design a less morbid rat model to explore the immunological obstacles of limb transplantation, and particularly skin. Twenty lower hindlimbs from 10 donors were transplanted into a heterotopic subcutaneous position into 20 animals (10 isogeneic and 10 allogeneic). Each group was further subdivided to include animals with (n = 5) and without (n = 5) a skin paddle for observation of cutaneous signs of rejection. All grafts in the isogeneic group survived for 100 days, i.e., the endpoint of the study. Allogeneic transplants rejected their allografts at a mean of 12.8 days (with skin) and 20.6 days (without). Our heterotopic limb transplantation model takes less time and is less stressful to the animals, while allowing for early observation of graft skin rejection, when compared to orthotopic whole-limb transplantation.
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