EURURO Vol. 71 No. 4

595 692

for GUVCA. Sopko and colleagues have elegantly used an
established model for peripheral mononuclear blood cell
(PMBC) activation called the mixed lymphocyte reaction
(MLR) to study whether allogenic blood cells are indeed
activated by contact with corpus cavernosum tissue, which
was harvested from patients undergoing penile prosthesis
implantation. In a small cohort of 10 tissue samples, they
illustrate that coculturing of allogenic—but not autolo-
gous—cavernosum tissue induces a global increase in
transplant-associated gene expression in PMBCs, and that
these changes are prevented by the addition of cyclosporine
A to the culture system. Conversely, histomorphometric
analysis of the cavernous tissue, both in fixed tissue as in
live imaging experiments, showed an influx of inflamma-
tory cells in allograft MLR, but not in autologous MLR, and
apoptosis was frequently seen in cavernous nerves and
smooth muscle cells in the cavernous tissues subjected to
allograft MLR. While it can be argued that these findings are
predictable, the authors interestingly performed functional
assays looking at in-vitro contractility of human cavernous
tissue, again after coincubation with PMBCs, and found that
allo-transplantation reduces contraction, and to a lesser
degree relaxation, in response to electrical field stimulation.
This is in contrast with findings in in-vivo transplant models
of the heart for example, where vasoconstriction of the
coronary arteries was found in vivo but could not be
elucidated in vitro . The exact mechanisms behind these
observations remain to be thoroughly investigated but may
include apoptosis of smooth muscle but also alterations in
contractile state as a result of release of a variety of
vasoactive compounds during the inflammatory reaction
. The impaired contractile and relaxant function of the
cavernous strips in vitro was rather contrarily worsened by
cyclosporine treatment, which may be a direct effect, as the
authors state that long term use of cyclosporine indeed
results in the development of hypertension and the
impairment of erectile function.
While these experiments provide preliminary clues on
the effects of both rejection and immunosuppression on
erectile tissue, the conclusions must be strengthened and
evidence expanded whilst working up a GUVCA clinical
protocol. First, in a sample size of 10 any confounding factor
can have a major impact. What is the effect of culturing
tissues ex-vivo on their contractility? This question may be
answered by adding an appropriate control (eg, freshly
isolated or noncultured tissue). Furthermore, the conclu-
sions are partially based on quantitative data (apoptosis,
leukocyte infiltration, and live laser confocal microscopy
experiments), which ideally should be confirmed by
performing quantitative molecular experiments such as
quantitative polymerase chain reaction. Additionally, the
experimental design gives clues on what immunological
reactions and effects thereof can be expected in the
hyperacute and acute phase, but not beyond these phases.
Whilst, as the authors correctly stated, in-vivo experiments
in previously described models do not allow for conclusions
on function, the isolated ex-vivo approach also has inherent
drawbacks as it does not mimic the complex in-vivo
environment and is less likely to adapt to externally
inflicted changes and injuries.
Notwithstanding these limitations inherent to the
disorder studied and the experimental design, the authors
are to be commended on their excellent achievement as
they, for the first time, give clues on the immunologic
complexity of allogeneic penile transplantation and the
effects thereof on erectile function. As part of a broader
project, this translational research endeavor helps to pave
the way for the many men who have been inspired by few
anecdotal stories, which have received unparalleled cover-
age of the lay press.
Conflicts of interest: The author has nothing to disclose.
Acknowledgments: Nikolai Sopko will highlight their findings and the
penile transplant development program at Johns Hopkins University
during the European Society of Sexual Medicine congress in Nice, France,
which will be held February 2–4, 2017.
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report of penile transplantation. Eur Urol 2006;50:851-3. Eur Urol
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