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Regenerative potential of human dental pulp stem cells in the treatment of stress urinary incontinence: In vitro and in vivo study

By 30 Novembre 2019Febbraio 3rd, 2022No Comments

Alessio Zordani, Alessandra Pisciotta, Laura Bertoni, Giulia Bertani, Antonio Vallarola, Daniela Giuliani, Stefano Puliatti, Daniela Mecugni, Giampaolo Bianchi, Anto de Pol, Gianluca Carnevale

Abstract

Objectives: To evaluate the regenerative potential of human dental pulp stem cells (hDPSCs) in an animal model of stress urinary incontinence (SUI). SUI, an involuntary leakage of urine, is due to physical stress involving an increase in bladder pressure and a damage of external urethral sphincter affecting muscles and nerves. Conventional therapies can only relieve the symptoms. Human DPSCs are characterized by peculiar stemness and immunomodulatory properties and might provide an alternative tool for SUI therapy.

Materials and methods: In vitro phase: hDPSCs were induced towards the myogenic commitment following a 24 hours pre-conditioning with 5-aza-2′-deoxycytidine (5-Aza), then differentiation was evaluated. In vivo phase: pudendal nerve was transected in female rats to induce stress urinary incontinence; then, pre-differentiated hDPSCs were injected in the striated urethral sphincter. Four weeks later, urethral sphincter regeneration was assayed through histological, functional and immunohistochemical analyses.

Results: Human DPSCs were able to commit towards myogenic lineage in vitro and, four weeks after cell injection, hDPSCs engrafted in the external urethral sphincter whose thickness was almost recovered, committed towards myogenic lineage in vivo, promoted vascularization and an appreciable recovery of the continence. Moreover, hDPSCs were detected within the nerve, suggesting their participation in repair of transected nerve.

Conclusions: These promising data and further investigations on immunomodulatory abilities of hDPSCs would allow to make them a potential tool for alternative therapies of SUI.

© 2019 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.

Conflict of interest statement

The authors declare that no conflict of interests exists.

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Stefano Puliatti

Stefano Puliatti

Il Dr. Puliatti si è laureato in Medicina e chirurgia nel 2012 presso l’Università degli Studi di Modena ed ha poi conseguito il titolo di specialista in Urologia con il massimo dei voti presso lo stesso Ateneo. Da Luglio 2019 ricopre il ruolo di Assistant Professor in Urologia presso l'Università di Modena e Reggio Emilia. Da Luglio 2019 ricopre anche il ruolo di Deputy Medical Director of ORSI Academy, Melle, Belgio e svolge attività clinica e chirurgica presso OLV (Onze Lieve Vrouwziekenhuis) Hospital in Aalst, Belgio (direttore: Prof. Alex Mottrie). La sua formazione si è incentrata in particolare sulla Chirurgia robotica e oncologica delle vie urinarie, avendo come principali campi di applicazione anche tumori e malattie della prostata, tumori del rene e delle alte vie urinarie, disturbi minzionali, calcolosi delle vie urinarie. È inoltre autore e coautore di articoli scientifici e capitoli di libro in ambito urologico. Attualmente svolge attività in libera professione presso diverse strutture situate a Modena e Provincia.