Muscle derived stem cell/alginate/polycaprolactone/injection therapy in rats with denervated urethral sphincter

Purpose: In this study, we tested whether injections of muscle-derived stem cells and alginate (Alg)/polycaprolactone (PCL) after denervation of the pudendal nerve could increase the leak point pressure (LPP) and closing pressure (CP) over the long term in a rat model of urinary incontinence. Materials and Methods: Muscle derived stern cells (MDSC) were isolated from the gastrocnemius muscle of normal female rats, and these cells were purified for creating a myogenic population by the preplate technique. In the denervated (D) group, the pudendal nerve was transected bilaterally via a dorsal incision in order to denervate the external urethral sphincter. The denervated external urethral sphincter was injected with Alg/PCL (AP group), or MDSC/Alg/PCL (M group) into the proximal urethra after pudendal nerve transection. At 1 and 3 months, the LPP and CP measurements were visually identified by using the vertical tilt/intravesical pressure clamp model of stress urinary incontinence. The rats were then sacrificed and their urethras were harvested for histology. Results: Both the LPP and CP were significantly lower in the denervated group at each time compared with the normal (N group), AP and M groups, and both the LPP and CP in the N, AP and M groups were significantly higher than those in the D group at both 1 and 3 months. The persistence of MDSC over the period of the study was verified by histology. Thus, pudendal nerve denervation led to a progressive decline in the LPP and CP that was evident at 1 month and this persisted to 3 months, and injection of MDSC/Alg/PCL into the denervated rats led to a long term increase in the LPP and CP. Conclusions: The N, AP and M groups all had significantly higher LPPs than the D group, and MDSC/Alg/PCL injection into the denervated external urethral sphincter in female rats increased the LPP and CP in both the short and long term. We also observed a long term bulking effect of MDSC/Alg/PCL injection in the stress incontinence animal model.