Intraurethral muscle-derived cell injections increase leak point pressure in a rat model of intrinsic sphincter deficiency

Objectives. To determine whether allogenic muscle-derived cells (MDCs) could restore sphincter function in rats with intrinsic sphincter deficiency (ISD). ISD denotes a malfunction of the urethral sphincter. Methods. ISD was produced in 25 adult female Sprague-Dawley rats by cauterizing tissues lateral to the mid-urethra. One week after cauterization, 1.5 X 10(6) MDCs, genetically engineered for beta-galactosidase expression, was injected into the mid-urethra in 16 rats. Another 9 rats were injected with Hanks' balanced salt solution after cauterization. As a control, 9 normal rats underwent a sham operation. Sphincter function was studied using the vertical tilt table/intravesical pressure clamp technique to measure leak point pressures (LPPs). The fate of the MDCs was assessed using LacZ staining. Results. The injection of MDCs increased the LPP without affecting bladder function. The mean LPP of the control rats 2, 4, and 6 weeks after the sham operation was 49.8 +/- 1.3, 51.2 +/- 1.5, and 51.6 +/- 2.0 cm H2O, respectively. The mean LPP of the rats 2, 4, and 6 weeks after cauterization and Hanks' balanced salt solution injection was 17.2 +/- 1.4, 26.9 +/- 1.9, and 25.5 +/- 1.3 cm H2O, respectively. The mean LPP of the rats 2, 4, and 6 weeks after cauterization and MDC injection was 38.2 +/- 2.2, 43.1 +/- 2.6, and 51.5 +/- 0.9 cm H2O, respectively. LacZ staining confirmed that MDC had integrated within the striated muscle layer of the cauterized urethra. Conclusions. The injection of intraurethral MDCs improved sphincter function in rats with ISD and may provide an attractive alternative to current treatments. (C) 2004 Elsevier Inc.