Improved Sphincter Muscle Regeneration by Myoblasts from M. extensor carpi radialis in a Large Animal Model of Urinary Incontinence

Purpose: Stress urinary incontinence (SUI) is a significant medical challenge affecting substantial parts of modern societies. Several studies suggested that cell therapy may alleviate the symptoms. However, in many cases, the overall efficacy was not satisfactory for the patient's needs. Moreover, in our recent preclinical studies, myoblasts isolated from M. semitendinosus failed to restore significant urethral sphincter function. We, therefore, investigated in our large animal SUI model whether myoblasts from other muscles yielded better sphincter recovery. Methods: Urethral sphincter deficiency was induced surgically in six female littermates and confirmed by measuring the urethral wall pressure. Three days after induction of sphincter deficiency in gilts, homologous myoblasts were injected into the sphincter complex. The urethral wall pressure and urine status were monitored weekly for a six-week follow-up. Results: Myoblasts isolated from M. extensor carpi radialis yielded a high expression of the myogenic markers desmin, CD56, ACTA1, MSTN, Myf6, and MyoD; were differentiation-competent; and formed myotubes in vitro. Such cells restored significant sphincter deficiency (2494 ± 266 U; ≙92%; p < 0.001; n = 6) and yielded a complete functional recovery from the induced sphincter deficiency (481 ± 123 U, ≙18%) when compared to the starting levels of untreated healthy pigs (2683 ± 764 U; ≙100%). The experimental group showed significant recovery compared to the mock controls (p < 0.045). Conclusions: The choice of myoblasts contributes to the clinical outcome in our large animal model of urinary incontinence. Myoblasts from M. extensor carpi radialis facilitated better sphincter recovery compared to myoblasts from M. semitendinosus.

Universitätsklinikum Tübingen