EURURO Vol. 71 No. 4

[1_TD$DIFF]

Platinum Priority – Reconstructive Urology

Editorial by Maarten Albersen on pp. 594–595 of this issue

Ex Vivo Model of Human Penile Transplantation and Rejection:

Implications for Erectile Tissue Physiology

Nikolai A. Sopko

a , y , * ,

Hotaka Matsui

b ,

, Denver M. Lough

c ,

Devin Miller

c ,

Kelly Harris

a ,

Max Kates

a ,

Xiaopu Liu

a ,

Kevin Billups

a ,

Richard Redett

c ,

Arthur L. Burnett

a ,

Gerald Brandacher

c ,

Trinity J. Bivalacqua

The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, MD;

Department

of Urology, Doai Memorial Hospital and The University of Tokyo, Tokyo, Japan;

Department of Plastic and Reconstructive Surgery, Vascularized Composite

Allotransplantation (VCA) Laboratory, The Johns Hopkins University School of Medicine, Baltimore, MD

E U R O P E A N U R O L O G Y 7 1 ( 2 0 1 7 ) 5 8 4 – 5 9 3

available at

www.scienced irect.com

journal homepage:

www.europeanurology.com

Article info

Article history:

Accepted July 4, 2016

Associate Editor:

Christian Gratzke

Keywords:

Penile transplantation

Erectile dysfunction

Tissue myography

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

M 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

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 trans-

plantation rejection. Tissue rejection impaired erectile tissue physiology. This report

suggests that cyclosporin A might hinder corporal physiology and that other immuno-

suppressant agents, such as FK506, might be better suited to penile transplantation.

Contributed equally to this work.

* Corresponding author. The Johns Hopkins Hospital, Marburg Bldg 420, 1800 Orleans Street,

Baltimore, MD 21287, USA. Tel. +1 410 614 0197; Fax: +1 410 614 3695.

E-mail address:

nas@jhmi.edu

(N.A. Sopko).

http://dx.doi.org/10.1016/j.eururo.2016.07.006

0302-2838/