• Denver M Lough, Nikolai A Sopko, Hotaka Matsui, Devin Miller, Edward W Swanson, Rachel Bluebond-Langner, Gerald Brandacher, Arthur L Burnett, Trinity J Bivalacqua, and Richard J Redett.
• From the Departments of Plastic and Reconstructive Surgery and Urologic Surgery, The Johns Hopkins University Hospital; and the Laboratory for Regenerative Medicine and Applied Sciences, Institute for Plastic and Reconstructive Surgery, Southern Illinois University School of Medicine.
• Plast. Reconstr. Surg. 2019 Mar 1; 143 (3): 534e-544e.

BackgroundAlthough significant surgical advances have been made in the form of microvascular surgery and autologous free tissue transfer, penile reconstruction still poses several difficult challenges. Although interest in penile vascularized composite allotransplantation has grown since the first attempted transplant in 2006, little is known regarding the kinetics of rejection and subsequent function of penile allografts. The penis contains multiple tissue types that are not qualified by the Banff 2007 vascularized composite allotransplantation classification system, including urogenital mucosal epithelium and erectile tissues. In this study, the authors investigate the propagation of rejection and the resultant function following rejection in rat and human penile tissues.MethodsRejected human and rat penile tissues were examined using an ex vivo real-time tissue-based derivative of the classic mixed lymphocyte reaction assay to determine the interactions occurring between en bloc penile tissues and peripheral blood mononuclear cells (autologous and allogeneic). Correlative in vivo heterotopic rat penile vascularized composite allotransplantation was used to correlate ex vivo findings.ResultsIn both human and rat ex vivo systems and in vivo rat vascularized composite allotransplantation, the urethral mucosa was the first to undergo rejection-associated apoptosis. The urethral mucosa was the most immunogenic and led to the highest level of peripheral blood mononuclear cell proliferative generations in all systems, whereas the neural tissues of the penis remained immune privileged.ConclusionThese findings are the first to describe the kinetics of rejection in both human and rat penile vascularized composite allotransplantation and that the urethral mucosa is the most antigenic, suffering the highest level of rejection-associated apoptosis and peripheral blood mononuclear cell proliferative aggregation.

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