TY - JOUR
T1 - The Urogenital Epithelium and Corporal Tissues Are the Primary Targets of Rejection in Penile Vascularized Composite Allotransplantation
T2 - A New Real-Time Tissue-Based Monitoring System
AU - Lough, Denver M.
AU - Sopko, Nikolai A.
AU - Matsui, Hotaka
AU - Miller, Devin
AU - Swanson, Edward W.
AU - Bluebond-Langner, Rachel
AU - Brandacher, Gerald
AU - Burnett, Arthur L.
AU - Bivalacqua, Trinity J.
AU - Redett, Richard J.
N1 - Publisher Copyright:
© 2019 Lippincott Williams and Wilkins. All rights reserved.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Background: Although 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. Methods: Rejected 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. Results: In 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. Conclusion: These 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.
AB - Background: Although 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. Methods: Rejected 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. Results: In 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. Conclusion: These 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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U2 - 10.1097/PRS.0000000000005377
DO - 10.1097/PRS.0000000000005377
M3 - Review article
C2 - 30817651
AN - SCOPUS:85064732850
SN - 0032-1052
VL - 143
SP - 534E-544E
JO - Plastic and reconstructive surgery
JF - Plastic and reconstructive surgery
IS - 3
ER -