Penile transplantation: an emerging option for genitourinary reconstruction.

Penile transplantation is an emerging option for patients with severe genital defects not amenable to traditional reconstructive options. In this article, we discuss the burgeoning problem of severe male genitourinary trauma in the military, the limitations of traditional reconstructive options in addressing these problems, and the potential for penile transplantation to provide improved outcomes. We also review the preclinical research and limited worldwide experience with penile transplantation to date, including lessons learned, and discuss the many important technical, logistical, and ethical considerations pertaining to penile transplantation that must be addressed to maximize the likelihood of successful implementation.

Diagnosing skin rejection in vascularized composite allotransplantation: advances and challenges.

Refinements in microsurgical techniques coupled with advances in immunosuppressive and immunomodulatory protocols have enabled broader clinical application of vascularized composite allotransplantation (VCA) with encouraging immunological, functional, and esthetic results. However, skin rejection remains a significant obstacle and a serious complication for VCA recipients. Clinical and histopathological features of rejection in VCA have been described in a number of studies, which led to the development of an international consensus on the classification guidelines of rejection in the context of VCA. Nevertheless, currently available diagnostic modalities still have several limitations and shortcomings that can pose a significant diagnostic challenge, particularly when signs of rejection are found to be equivocal. In this review, we provide a critical analysis of these advances and challenges in diagnosing skin rejection. Specifically, we highlight the gaps in understanding of rejection mechanisms, the shortfalls in correlating cellular, molecular, and clinicopathologic markers with rejection grades, deficiencies in defining chronic rejection, and antibody-mediated rejection after VCA, as well as providing an outlook on novel concepts, such as the utilization of advanced computational analyses and cross-disciplinary diagnostic approaches.

Stable mixed hematopoietic chimerism permits tolerance of vascularized composite allografts across a full major histocompatibility mismatch in swine.

This study tested the hypothesis that vascularized composite allografts (VCA) could be accepted in a robust model of hematopoietic chimerism by injecting allogeneic bone marrow cells (BMC) into swine fetuses. Outbred Yorkshire sows and boars were screened to ensure the absence of the major histocompatibility (MHC) allele SLA(cc) of inbred MGH miniature swine and then mated. Bone marrow harvested from an SLA(cc) swine donor was T-cell depleted and injected intravenously into the fetuses between days 50-55 of gestation. After birth, the piglets were studied with flow cytometry to detect donor cells and mixed lymphocyte reactions (MLR) and cell-mediated lympholysis (CML) assays to assess their response to donor. Donor-matched VCAs from SLA(cc) donors were performed on four chimeric and two nonchimeric swine. The results showed donor cell engraftment and multilineage macrochimerism after the in utero transplantation of adult BMC, and chimeric animals were unresponsive to donor antigens in vitro. Both control VCAs were rejected by 21 days and were alloreactive. Chimeric animals accepted the VCAs and never developed antidonor antibodies or alloreactivity to donor. These results confirm that the intravascular, in utero transplantation of adult BMC leads to donor cell chimerism and donor-specific tolerance of VCAs across a full MHC barrier in this animal model.

Overcoming cross-gender differences and challenges in Le Fort-based, craniomaxillofacial transplantation with enhanced computer-assisted technology.

BACKGROUND: Sex-specific anthropometrics, skin texture/adnexae mismatch, and social apprehension have prevented cross-gender facial transplantation from evolving. However, the scarce donor pool and extreme waitlist times are currently suboptimal. Our objective was to (1) perform and assess cadaveric facial transplantation for each sex-mismatched scenario using virtual planning with cutting guide fabrication and (2) review the advantages/disadvantages of cross-gender facial transplantation. METHODS: Cross-gender facial transplantation feasibility was evaluated through 2 mock, double-jaw, Le Fort-based cadaveric allotransplants, including female donor-to-male recipient and male donor-to-female recipient. Hybrid facial-skeletal relationships were investigated using cephalometric measurements, including sellion-nasion-A point and sellion-nasion-B point angles, and lower-anterior-facial-height to total-anterior-facial-height ratio. Donor and recipient cutting guides were designed with virtual planning based on our team's experience in swine dissections and used to optimize the results. RESULTS: Skeletal proportions and facial-aesthetic harmony of the transplants (n = 2) were found to be equivalent to all reported experimental/clinical sex-matched cases by using custom guides and Mimics technology. Cephalometric measurements relative to Eastman Normal Values are shown. CONCLUSIONS: On the basis of our results, we believe that cross-gender facial transplantation can offer equivalent, anatomical skeletal outcomes to those of sex-matched pairs using preoperative planning and custom guides for execution. Lack of literature discussion of cross-gender facial transplantation highlights the general stigmata encompassing the subject. We hypothesize that concerns over sex-specific anthropometrics, skin texture/adnexae disparity, and increased immunological resistance have prevented full acceptance thus far. Advantages include an increased donor pool with expedited reconstruction, as well as size-matched donors.

Animal models for basic and translational research in reconstructive transplantation.

Reconstructive transplantation represents a bona fide option for select patients with devastating tissue loss, which could better restore the appearance, anatomy, and function than any other conventional treatment currently available. Despite favorable outcomes, broad clinical application of reconstructive transplantation is limited by the potential side effects of chronic multidrug immunosuppression. Thus, any reconstructive measures to improve these non-life-threatening conditions must address a delicate balance of risks and benefits. Today, several exciting novel therapeutic strategies, such as the implementation of cellular therapies including bone marrow or stem cells that integrate the concepts of immune regulation with those of nerve regeneration, are on the horizon. The development of reliable and reproducible small and large animal models is essential for the study of the unique immunological and biological aspects of vascularized composite allografts and to translate such novel immunoregulatory and tolerance-inducing strategies and therapeutic concepts from the bench to bedside. This review provides an overview of the multitude of small and large animal models that have been particularly designed for basic and translational research related to reconstructive transplantation.