V Sceberras1, E Attico2, E Bianchi2, G Galaverni2, M Melonari2, F Corradini2, M Fantacci2, A Ribbene2, L Losi2, S Balò3, M Lazzeri4, C Trombetta5, M Rizzo5, R Manfredini2, G Barbagli3, G Pellegrini6,7. 1. Holostem Terapie Avanzate, Via Gottardi 100, Modena, Italy. 2. Interdepartmental Centre for Regenerative Medicine "Stefano Ferrari", University of Modena e Reggio Emilia, Via Gottardi 100, Modena, Italy. 3. Centro Chirurgico Toscano, Via dei Lecci 22, Arezzo, Italy. 4. Istituto Clinico Humanitas IRCCS, Clinical and Research Hospital (MI), Rozzano, Italy. 5. Department of Urology of Cattinara Hospital, University of Trieste, Strada Fiume 447, Trieste, Italy. 6. Interdepartmental Centre for Regenerative Medicine "Stefano Ferrari", University of Modena e Reggio Emilia, Via Gottardi 100, Modena, Italy. graziella.pellegrini@unimore.it. 7. Holostem Terapie Avanzate, Via Gottardi 100, Modena, Italy. graziella.pellegrini@unimore.it.
Abstract
PURPOSE: This paper explores the feasibility of a new therapy for the treatment of hypospadias patients. Hypospadias is a very common congenital malformation of male genitals, with very high rate of recurrences after surgery. The field of regenerative medicine, which offers innovative solutions for many pathologies, still does not offer reliable solution for this pathology. Here, we propose quality, safety, and clinical feasibility assessment for an oral mucosa advanced therapy medicinal product (ATMP) grown on a biocompatible scaffold for a clinical study on urethral reconstruction of hypospadias patients. METHODS: Urethral and oral mucosal epithelia from donor biopsies were cultivated between two fibrin layers, under clinical-grade conditions for cell and tissue characterization and comparison, aimed at tissue engineering. In addition, single-clone analyses were performed to analyze gene expression profiles of the two epithelia by microarray technology. RESULTS: Oral mucosa appeared suitable for urethral reconstruction. The resulting ATMP was proven to maintain stem cells and regenerative potency. The preclinical safety studies were performed on human tissues to assess abnormalities and tumorigenicity, and confirmed the safety of the ATMP. Finally, the patient selection and the clinical protocol for the upcoming clinical trial were defined. CONCLUSIONS: Against this backdrop, in this paper, we are proposing a new reproducible and reliable ATMP for the treatment of hypospadias.
PURPOSE: This paper explores the feasibility of a new therapy for the treatment of hypospadiaspatients. Hypospadias is a very common congenital malformation of male genitals, with very high rate of recurrences after surgery. The field of regenerative medicine, which offers innovative solutions for many pathologies, still does not offer reliable solution for this pathology. Here, we propose quality, safety, and clinical feasibility assessment for an oral mucosa advanced therapy medicinal product (ATMP) grown on a biocompatible scaffold for a clinical study on urethral reconstruction of hypospadiaspatients. METHODS: Urethral and oral mucosal epithelia from donor biopsies were cultivated between two fibrin layers, under clinical-grade conditions for cell and tissue characterization and comparison, aimed at tissue engineering. In addition, single-clone analyses were performed to analyze gene expression profiles of the two epithelia by microarray technology. RESULTS: Oral mucosa appeared suitable for urethral reconstruction. The resulting ATMP was proven to maintain stem cells and regenerative potency. The preclinical safety studies were performed on human tissues to assess abnormalities and tumorigenicity, and confirmed the safety of the ATMP. Finally, the patient selection and the clinical protocol for the upcoming clinical trial were defined. CONCLUSIONS: Against this backdrop, in this paper, we are proposing a new reproducible and reliable ATMP for the treatment of hypospadias.
Authors: Reynaldo G Gómez; Laura G Velarde; Rodrigo A Campos; Alvaro A Saavedra; Erico J Delgado; Richard A Santucci; Kyle A Scarberry Journal: World J Urol Date: 2020-08-18 Impact factor: 4.226