Mp28-14 Novel in Vivo Peyronie's Patient-Derived Xenograft Model Recapitulates Human Curvature in Immunocompromised Rats

You have accessJournal of UrologySexual Function/Dysfunction: Peyronie's Disease (MP28)1 May 2024MP28-14 NOVEL IN VIVO PEYRONIE'S PATIENT-DERIVED XENOGRAFT MODEL RECAPITULATES HUMAN CURVATURE IN IMMUNOCOMPROMISED RATS Garrett Brinkley, Jacob W. Greenberg, Danish Singh, Asim B. Abdel-Mageed, and Wayne J. G. Hellstrom Garrett BrinkleyGarrett Brinkley , Jacob W. GreenbergJacob W. Greenberg , Danish SinghDanish Singh , Asim B. Abdel-MageedAsim B. Abdel-Mageed , and Wayne J. G. HellstromWayne J. G. Hellstrom View All Author Informationhttps://doi.org/10.1097/01.JU.0001008872.42208.7a.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Peyronie's disease (PD) is a psychologically debilitating and physically limiting condition with∼4% prevalence in the adult male population. Currently, there are few nonsurgical options, with paucity linked to the limited pool of validated animal models available for preclinical research. Available models do not mirror the human PD tissue microenvironment of origin but rather simulate TGF-β plaque pathophysiology. To address this issue, for the first time, this study aimed to form a translational, preclinical, patient-derived xenograft (PDX) animal model mimicking human PD pathogenesis that can be employed as a predictive model for drug development. METHODS: In compliance with institutional-approved protocols and appropriate consent, fresh Peyronie's plaques were excised from human patients and subsequently implanted into the tunica albuginea of two immunocompromised (nude) rats. Rodents were followed for 3 months. Curvature was then assessed by using saline injected through a 28-gauge needle into the lateral side of the corpora. Curvature was measured from midline proximal to the distal aspect of the point of maximal curvature. Penile tissue was harvested, and the specimen was fixed in formalin, sectioned, then stained with H&E. RESULTS: A total of two rats were implanted with a Peyronie's PDX, but only one PDX survived for 3 months. Artificial erection with normal saline demonstrated a 32° curvature (Figure 1a). The tissue was sent for histologic evaluation. H&E staining demonstrated persistent plaque on the dorsolateral aspect of the penial shaft adjacent to the dorsal vein and nerve bundle. The plaque can further be identified in-line with the Buck's facia, invading the tunica albuginea (Figure 1b). CONCLUSIONS: PD is challenging to treat with standard care, including collagenase injections, plication, incision and grafting, and penile prosthesis placement. There is an imminent need to validate available therapies, optimize current strategies, and provide new treatment options. Management of this disease will not progress without new animal models. This pilot study (that recapitulates the in vivo human plaque microenvironment) validates the feasibility of developing a PDX animal model for human PD with curvature. Additional optimization analysis warrants further investigation in future studies. Download PPT Source of Funding: No funding © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e477 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Garrett Brinkley More articles by this author Jacob W. Greenberg More articles by this author Danish Singh More articles by this author Asim B. Abdel-Mageed More articles by this author Wayne J. G. Hellstrom More articles by this author Expand All Advertisement PDF downloadLoading ...