Transurethral Myoblast Injection for Urinary Incontinence in Children With Bladder Exstrophy

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Achieving urinary continence in patients with bladder extrophy epispadias complex remains a challenging urological goal. Children with bladder extrophy epispadias complex generally undergo many surgical procedures for the treatment of sphincteric incompetence, including bladder neck reconstruction, ...

Achieving urinary continence in patients with bladder extrophy epispadias complex remains a challenging urological goal. Children with bladder extrophy epispadias complex generally undergo many surgical procedures for the treatment of sphincteric incompetence, including bladder neck reconstruction, slings and bulking agent injection. The key point in most of these procedures is to enhance urethral resistance, leading to some degree of bladder outlet obstruction. However, the reported 7% to 85% continence rates in these patients may not exactly represent those children who achieve volitional voiding through the urethra, but may also include the ones with bladder augmentation and urinary diversion. Endoscopic injection of bulking agent has emerged as a therapeutic approach in the treatment of urinary incontinence (UI). this procedure seems to be economical, with shorter hospitalization and fewer major complications. On the other hand, degradation, migration, reabsorption, overbulking, bladder outlet obstruction and hypersensitivity are frequently reported complications of bulking agents. The ideal substance for periurethral injection should be durable, non immunogenic, nonmigratory and efficacious. So, transurethral implantation of autologous myoblasts may represent an improved alternative to synthetic bulking agents, with the unique ability to compensate for the deficient muscle fibers in the urethral sphincter. Patients with incontinence usually have decreased resting tone and contractility of the rhabdosphincter. In patients with bladder extrophy epispadias complex the perineal structures are dislocated laterally, and the internal and external urethral sphincters are deficient. Muscle precursor cells constantly regenerate striated muscles, and include the quiescent satellite cells located beneath the basal lamina of skeletal myofibers, which are responsible for repair of the terminally differentiated striated muscle tissue. After injury or in response to intensive physical exercise satellite cells proliferate and differentiate into myoblasts, which ultimately fuse to form new myofibers capable of muscle contraction. Considering the limited capacity of the rhabdosphincter for regeneration, the idea of urethral sphincter repair in patients with bladder extrophy epispadias COMPLEX via transurethral injection of autologous myoblasts has been suggested. The technical availability of these cells, as well as immunological acceptance and survival, makes them appropriate for this purpose. Satellite cells are committed cell lineage with restricted plasticity and do not multiply beyond the required repair needs. This property confers an acceptable measure of safety for clinical applications. The first clinical study of cell therapy based treatment of sphincter insufficiency, using muscle derived stem cell transplantation was carried out in patients with stress incontinence revealed and confirmed the ability of cell therapy to improve the structure and contractile function of the sphincter.

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