USC-Exos in Corpus Spongiosum Reconstruction for Hypospadias

A Study on the Value of Autologous Exosomes Secreted by Urine-derived Stem Cell (USC-Exos) in Corpus Spongiosum Reconstruction for Hypospadias

Hypospadias is one of the common congenital malformation disorders in male children, with a ratio of about 1 to 300 in newborn boys. Proximal hypospadias, due to the underdeveloped corpus spongiosum, has a high incidence of postoperative complications (e.g., urethral fistula, stricture, recurrence of penile curvature), exceeding 50%. Traditional surgeries focus on urethral tubularization but fail to restore the corpus spongiosum, leading to long-term micturition and sexual dysfunction.

Recent studies have shown that stem cell exosomes promote angiogenesis and tissue repair through paracrine mechanisms. Urine-derived stem cells (USC) have the advantages of non-invasive acquisition and high proliferative capacity, and the investigator's previous study found that the USCs secreted exosomes (USC-Exos) promoted the regeneration of cavernous sinusoids in an animal model. In this study, the investigators applied autologous USC-Exos for the first time to pediatric hypospadias surgery to evaluate its clinical value in corpus spongiosum reconstruction.

Study Overview

• Status: Completed
• Conditions: Hypospadias
• Intervention / Treatment: Procedure: Exsome; Procedure: Placebo

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Shanghai Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 46, XY karyotype
• proximal hypospadias
• treated with Byar staged surgery
• informed consent from guardians.

Exclusion Criteria:

• patients with sexual development disorders
• those undergoing one-stage repair
• patients or guardians refusing participation
• those lost to follow-up

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: exosome group; Children with proximal hypospadias admitted to the Department of Urology of Shanghai Children's Hospital Inclusion criteria: 46, XY karyotype; treated with Byar staged surgery; and informed consent from guardians. Exclusion criteria: patients with sexual development disorders; those undergoing one-stage repair; patients or guardians refusing participation; and those lost to follow-up.	Procedure: Exsome; 200 ml of urine was collected by aseptic catheterization, after which it was centrifuged and expanded to the P6 generation using a gelatin-coated culture plate. Exosome extraction: USC-Exos was isolated via tangential flow filtration combined with ultrafiltration. Quality control was performed via nano-flow cytometry (particle size 72.27±21.90 nm), transmission electron microscopy (double-membrane structure), and Western blot (positive for CD9/CD63/TSG101). First stage, the dorsal penile foreskin flap was transferred to the ventral side to reconstruct the urethral plate (Byar Stage Ⅰ). In the exosome group, USC-Exos (1-3×10^10^/ml) were applied topically. Second-stage, urethral tubularization after 6-9 months, urethral plate tissues were taken for HE, CD31, α-SMA and VEGF immunohistochemical analysis during the surgery.
Placebo Comparator: Control group; Use the sodium hyaluronate	Procedure: Placebo; First stage, the dorsal penile foreskin flap was transferred to the ventral side to reconstruct the urethral plate (Byar Stage Ⅰ). In the control group, sodium hyaluronate was used. Second-stage, urethral tubularization after 6-9 months, urethral plate tissues were taken for HE, CD31, α-SMA and VEGF immunohistochemical analysis during the surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
100% participants treated with the staged surgery	82 participants were average divided into Exosome and Control group. All the participants were treated with the Byar's staged surgery(including I and II stage).	From enrollment to the 6 months after the second stage surgery

Collaborators and Investigators

• Sponsor: Shanghai Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): September 30, 2025
• Study Completion (Actual): December 31, 2025

Study Registration Dates

• First Submitted: March 1, 2026
• First Submitted That Met QC Criteria: March 22, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 22, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: hypospadias; exosome; corpus spongiosum; urethral reconstruction; urine-derived stem cell
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Diseases, Male; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Congenital Abnormalities; Urogenital Abnormalities; Penile Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hypospadias
• Other Study ID Numbers: SHDC2020CR3013A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No