Login to Access Video or Poster Abstract: MP26-11
Sources of Funding: NIH NIDDK R56 DK100669-01A1

Introduction

Insulin-like growth factor-1 (IGF-1) treatment has been reported to accelerate recovery from stress urinary incontinence (SUI) induced by simulated childbirth injury in rats. However, a local sustained delivery method is ideal for further clinical applications to avoid side effects of IGF-1. The goal of this study was to determine the effects of controlled release of IGF1 from alginate-gelatin microbeads (IGF1-A-G-beads) on sphincter tissue repair in a rat model of stress urinary incontinence (SUI).

Methods

Forty-four female Sprague-Dawley rats were divided into 4 equal groups: sham vaginal distension (VD) + saline, VD + saline, VD + empty A-G-beads, & VD + IGF1-A-G-beads). All rats received periurethral injections of A-G-beads immediately after VD. Leak point pressure (LPP) testing and external urethral sphincter (EUS) electromyography (EMG) were performed 1 week later. Urethral tissue and anterior vagina were dissected en bloc for further analysis via histology and immunofluorescence. Quantitative data was analyzed using ANOVA on Ranks followed by a Tukey posthoc test with p < 0.05 indicating a statistically significant difference between groups. Data is presented as mean +/- standard error of the mean.

Results

LPP was significantly decreased 1 week after VD treated with saline only (23.9 ± 1.3 cmH2O) compared to sham VD (44.4 ± 3.4 cmH2O). LPP was also significantly decreased in the VD + empty A-G-beads group (21.7 ± 0.8 cmH2O) compared to sham VD, demonstrating that the microbeads themselves do not create a bulking or obstructive effect in the urethra. In contrast, rats with VD treated with IGF1-A-G-beads (28.4 ± 1.2 cmH2O) was significantly greater than LPP of rats with VD treated with empty A-G-beads and had LPP partway between and not significantly different from either the sham VD or the VD + saline groups, demonstrating initiation of a reparative effect 1 week after VD. The increase in EUS EMG amplitude with LPP testing was significantly reduced after VD treated with saline or empty A-G-beads compared to sham VD. VD rats treated with IGF1-A-G-beads had EUS EMG amplitude response to LPP testing partway between and not significantly different from either the sham VD or VD + saline groups. Histological analysis demonstrated well-developed, well-organized skeletal muscle fibers in the external urethral sphincter in the VD + IGF1-A-G-beads group, similar to that of sham VD rats. In contrast, substantial muscle fiber attenuation and disorganization was observed in VD rats treated with saline or empty A-G-beads.

Conclusions

IGF1-A-G-beads improved recovery in a rat model of SUI, suggesting that these microspheres could provide a local sustained delivery method for IGF-1.

Funding

NIH NIDDK R56 DK100669-01A1