Characterization of Clinical and Histological Rejection of Male Genital Tissues Using a Novel Microsurgical Rat Penile Transplantation Model

Samuel A.J. Fidder, Georg J. Furtmüller, Brian Simons, Byoung Chol Oh, Maria Chicco, Joanna W. Etra, Cory Brayton, Carisa M. Cooney, Dalibor Vasilic, Barbara Kern, Denver Lough, W. P.Andrew Lee, Richard J. Redett, Gerald Brandacher, Damon S. Cooney

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Penis transplantation represents an exciting new avenue for restoration of male urogenitalia. However, little is known about the specific immunological features of penile transplants, limiting their application in complex urogenital reconstruction. To properly study this emerging form of transplantation, adequate preclinical models are a necessity. The purpose of this study is to establish a clinical and histological rejection classification of urogenital tissue transplants using a new rat heterotopic penile transplant model that includes preputial skin. METHODS: Syngeneic and allogeneic heterotopic penile transplantations were performed on Lewis and Brown Norway rats using a new model designed by our group. Grafts were clinically and histologically monitored at postoperative days (POD) 3-30. RESULTS: Six syngeneic and 25 allogeneic transplants were performed. All syngeneic and tacrolimus-treated grafts survived until endpoint. Allogeneic graft rejection is shown to follow a 4-stage clinical progression with all untreated allografts developing epidermal sloughing at POD7 and full rejecting between POD14 and POD16. Histological samples were used to develop a specific 4-grade rejection classification analogous to the 2007 Banff Criteria for skin-containing allografts. CONCLUSIONS: Graft skin and urethral lining tissue are first rejection targets followed by tunica albuginea and corpora cavernosa in a distal to proximal pattern. We established a robust and reproducible murine model to study the immunobiology of male genital tissue in the context of transplantation and developed a novel 4-grade clinical and histological rejection scale based on graft skin and urethral lining as the main targets of rejection.

Original languageEnglish (US)
Pages (from-to)2245-2254
Number of pages10
JournalTransplantation
Volume103
Issue number11
DOIs
StatePublished - Nov 1 2019
Externally publishedYes

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Transplantation
Transplants
Skin
Allografts
Heterotopic Transplantation
Homologous Transplantation
Penis
Graft Rejection
Tacrolimus

ASJC Scopus subject areas

  • Transplantation

Cite this

Fidder, S. A. J., Furtmüller, G. J., Simons, B., Oh, B. C., Chicco, M., Etra, J. W., ... Cooney, D. S. (2019). Characterization of Clinical and Histological Rejection of Male Genital Tissues Using a Novel Microsurgical Rat Penile Transplantation Model. Transplantation, 103(11), 2245-2254. https://doi.org/10.1097/TP.0000000000002812

Characterization of Clinical and Histological Rejection of Male Genital Tissues Using a Novel Microsurgical Rat Penile Transplantation Model. / Fidder, Samuel A.J.; Furtmüller, Georg J.; Simons, Brian; Oh, Byoung Chol; Chicco, Maria; Etra, Joanna W.; Brayton, Cory; Cooney, Carisa M.; Vasilic, Dalibor; Kern, Barbara; Lough, Denver; Lee, W. P.Andrew; Redett, Richard J.; Brandacher, Gerald; Cooney, Damon S.

In: Transplantation, Vol. 103, No. 11, 01.11.2019, p. 2245-2254.

Research output: Contribution to journalArticle

Fidder, SAJ, Furtmüller, GJ, Simons, B, Oh, BC, Chicco, M, Etra, JW, Brayton, C, Cooney, CM, Vasilic, D, Kern, B, Lough, D, Lee, WPA, Redett, RJ, Brandacher, G & Cooney, DS 2019, 'Characterization of Clinical and Histological Rejection of Male Genital Tissues Using a Novel Microsurgical Rat Penile Transplantation Model', Transplantation, vol. 103, no. 11, pp. 2245-2254. https://doi.org/10.1097/TP.0000000000002812
Fidder, Samuel A.J. ; Furtmüller, Georg J. ; Simons, Brian ; Oh, Byoung Chol ; Chicco, Maria ; Etra, Joanna W. ; Brayton, Cory ; Cooney, Carisa M. ; Vasilic, Dalibor ; Kern, Barbara ; Lough, Denver ; Lee, W. P.Andrew ; Redett, Richard J. ; Brandacher, Gerald ; Cooney, Damon S. / Characterization of Clinical and Histological Rejection of Male Genital Tissues Using a Novel Microsurgical Rat Penile Transplantation Model. In: Transplantation. 2019 ; Vol. 103, No. 11. pp. 2245-2254.
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abstract = "BACKGROUND: Penis transplantation represents an exciting new avenue for restoration of male urogenitalia. However, little is known about the specific immunological features of penile transplants, limiting their application in complex urogenital reconstruction. To properly study this emerging form of transplantation, adequate preclinical models are a necessity. The purpose of this study is to establish a clinical and histological rejection classification of urogenital tissue transplants using a new rat heterotopic penile transplant model that includes preputial skin. METHODS: Syngeneic and allogeneic heterotopic penile transplantations were performed on Lewis and Brown Norway rats using a new model designed by our group. Grafts were clinically and histologically monitored at postoperative days (POD) 3-30. RESULTS: Six syngeneic and 25 allogeneic transplants were performed. All syngeneic and tacrolimus-treated grafts survived until endpoint. Allogeneic graft rejection is shown to follow a 4-stage clinical progression with all untreated allografts developing epidermal sloughing at POD7 and full rejecting between POD14 and POD16. Histological samples were used to develop a specific 4-grade rejection classification analogous to the 2007 Banff Criteria for skin-containing allografts. CONCLUSIONS: Graft skin and urethral lining tissue are first rejection targets followed by tunica albuginea and corpora cavernosa in a distal to proximal pattern. We established a robust and reproducible murine model to study the immunobiology of male genital tissue in the context of transplantation and developed a novel 4-grade clinical and histological rejection scale based on graft skin and urethral lining as the main targets of rejection.",
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T1 - Characterization of Clinical and Histological Rejection of Male Genital Tissues Using a Novel Microsurgical Rat Penile Transplantation Model

AU - Fidder, Samuel A.J.

AU - Furtmüller, Georg J.

AU - Simons, Brian

AU - Oh, Byoung Chol

AU - Chicco, Maria

AU - Etra, Joanna W.

AU - Brayton, Cory

AU - Cooney, Carisa M.

AU - Vasilic, Dalibor

AU - Kern, Barbara

AU - Lough, Denver

AU - Lee, W. P.Andrew

AU - Redett, Richard J.

AU - Brandacher, Gerald

AU - Cooney, Damon S.

PY - 2019/11/1

Y1 - 2019/11/1

N2 - BACKGROUND: Penis transplantation represents an exciting new avenue for restoration of male urogenitalia. However, little is known about the specific immunological features of penile transplants, limiting their application in complex urogenital reconstruction. To properly study this emerging form of transplantation, adequate preclinical models are a necessity. The purpose of this study is to establish a clinical and histological rejection classification of urogenital tissue transplants using a new rat heterotopic penile transplant model that includes preputial skin. METHODS: Syngeneic and allogeneic heterotopic penile transplantations were performed on Lewis and Brown Norway rats using a new model designed by our group. Grafts were clinically and histologically monitored at postoperative days (POD) 3-30. RESULTS: Six syngeneic and 25 allogeneic transplants were performed. All syngeneic and tacrolimus-treated grafts survived until endpoint. Allogeneic graft rejection is shown to follow a 4-stage clinical progression with all untreated allografts developing epidermal sloughing at POD7 and full rejecting between POD14 and POD16. Histological samples were used to develop a specific 4-grade rejection classification analogous to the 2007 Banff Criteria for skin-containing allografts. CONCLUSIONS: Graft skin and urethral lining tissue are first rejection targets followed by tunica albuginea and corpora cavernosa in a distal to proximal pattern. We established a robust and reproducible murine model to study the immunobiology of male genital tissue in the context of transplantation and developed a novel 4-grade clinical and histological rejection scale based on graft skin and urethral lining as the main targets of rejection.

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