TY - JOUR
T1 - Ex Vivo Model of Human Penile Transplantation and Rejection
T2 - Implications for Erectile Tissue Physiology
AU - Sopko, Nikolai A.
AU - Matsui, Hotaka
AU - Lough, Denver M.
AU - Miller, Devin
AU - Harris, Kelly
AU - Kates, Max
AU - Liu, Xiaopu
AU - Billups, Kevin
AU - Redett, Richard
AU - Burnett, Arthur L.
AU - Brandacher, Gerald
AU - Bivalacqua, Trinity J.
N1 - Publisher Copyright:
© 2016 European Association of Urology
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Background Penile transplantation is a potential treatment option for severe penile tissue loss. Models of human penile rejection are lacking. Objective Evaluate effects of rejection and immunosuppression on cavernous tissue using a novel ex vivo mixed lymphocyte reaction (MLR) model. Design, setting, and participants Cavernous tissue and peripheral blood mononuclear cells (PBMCs) from 10 patients undergoing penile prosthesis operations and PBMCs from a healthy volunteer were obtained. Ex vivo MLRs were prepared by culturing cavernous tissue for 48 h in media alone, in media with autologous PBMCs, or in media with allogenic PBMCs to simulate control, autotransplant, and allogenic transplant conditions with or without 1 μM cyclosporine A (CsA) or 20 nM tacrolimus (FK506) treatment. Outcome measurements and statistical analysis Rejection was characterized by PBMC flow cytometry and gene expression transplant array. Cavernous tissues were evaluated by histomorphology and myography to assess contraction and relaxation. Data were analyzed using two-way analysis of variance and unpaired Student t test. Results and limitations Flow cytometry and tissue array demonstrated allogenic PBMC activation consistent with rejection. Rejection impaired cavernous tissue physiology and was associated with cellular infiltration and apoptosis. CsA prevented rejection but did not improve tissue relaxation. CsA treatment impaired relaxation in tissues cultured without PBMCs compared with media and FK506. Study limitations included the use of penile tissue with erectile dysfunction and lack of cross-matching data. Conclusions This model could be used to investigate the effects of penile rejection and immunosuppression. Additional studies are needed to optimize immunosuppression to prevent rejection and maximize corporal tissue physiology. Patient summary This report describes a novel ex vivo model of human penile transplantation rejection. Tissue rejection impaired erectile tissue physiology. This report suggests that cyclosporin A might hinder corporal physiology and that other immunosuppressant agents, such as FK506, might be better suited to penile transplantation.
AB - Background Penile transplantation is a potential treatment option for severe penile tissue loss. Models of human penile rejection are lacking. Objective Evaluate effects of rejection and immunosuppression on cavernous tissue using a novel ex vivo mixed lymphocyte reaction (MLR) model. Design, setting, and participants Cavernous tissue and peripheral blood mononuclear cells (PBMCs) from 10 patients undergoing penile prosthesis operations and PBMCs from a healthy volunteer were obtained. Ex vivo MLRs were prepared by culturing cavernous tissue for 48 h in media alone, in media with autologous PBMCs, or in media with allogenic PBMCs to simulate control, autotransplant, and allogenic transplant conditions with or without 1 μM cyclosporine A (CsA) or 20 nM tacrolimus (FK506) treatment. Outcome measurements and statistical analysis Rejection was characterized by PBMC flow cytometry and gene expression transplant array. Cavernous tissues were evaluated by histomorphology and myography to assess contraction and relaxation. Data were analyzed using two-way analysis of variance and unpaired Student t test. Results and limitations Flow cytometry and tissue array demonstrated allogenic PBMC activation consistent with rejection. Rejection impaired cavernous tissue physiology and was associated with cellular infiltration and apoptosis. CsA prevented rejection but did not improve tissue relaxation. CsA treatment impaired relaxation in tissues cultured without PBMCs compared with media and FK506. Study limitations included the use of penile tissue with erectile dysfunction and lack of cross-matching data. Conclusions This model could be used to investigate the effects of penile rejection and immunosuppression. Additional studies are needed to optimize immunosuppression to prevent rejection and maximize corporal tissue physiology. Patient summary This report describes a novel ex vivo model of human penile transplantation rejection. Tissue rejection impaired erectile tissue physiology. This report suggests that cyclosporin A might hinder corporal physiology and that other immunosuppressant agents, such as FK506, might be better suited to penile transplantation.
KW - Erectile dysfunction
KW - Penile transplantation
KW - Tissue myography
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U2 - 10.1016/j.eururo.2016.07.006
DO - 10.1016/j.eururo.2016.07.006
M3 - Article
C2 - 27432525
AN - SCOPUS:85002819842
SN - 0302-2838
VL - 71
SP - 584
EP - 593
JO - European Urology
JF - European Urology
IS - 4
ER -