Ex Vivo Model of Human Penile Transplantation and Rejection: Implications for Erectile Tissue Physiology

Nikolai A. Sopko, Hotaka Matsui, Denver M. Lough, Devin Miller, Kelly Harris, Max Kates, Xiaopu Liu, Kevin Lenuell Billups, Richard Redett, Arthur Burnett, Gerald Brandacher, Trinity Bivalacqua

Research output: Contribution to journalArticle

Abstract

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. Penile transplant models are lacking, and it is unknown how rejection and immunosuppression affect erectile physiology. Ex vivo mixed lymphocyte reaction simulates transplantation and demonstrated that rejection and certain immunosuppression treatments, such as cyclosporine A, impair erectile function.

Original languageEnglish (US)
JournalEuropean Urology
DOIs
StateAccepted/In press - 2016

Keywords

  • Erectile dysfunction
  • Penile transplantation
  • Tissue myography

ASJC Scopus subject areas

  • Urology

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