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  • Title: Intraurethral muscle-derived cell injections increase leak point pressure in a rat model of intrinsic sphincter deficiency.
    Author: Chermansky CJ, Tarin T, Kwon DD, Jankowski RJ, Cannon TW, de Groat WC, Huard J, Chancellor MB.
    Journal: Urology; 2004 Apr; 63(4):780-5. PubMed ID: 15072911.
    Abstract:
    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.
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