Long term effects of muscle-derived stem cells on leak point pressure and closing pressure in rats with transected pudendal nerves.

The survival of muscle-derived cells injected into the urethra and bladder wall was described recently. In this study, we tested whether injections of periurethral muscle-derived stem cells (MDSC) and bovine collagen (BC) after denervation of the pudendal nerve could increase leak point pressure (LPP) and closing pressure (CP) in female rats over the long term. S-D rats were anesthetized with halothane and the pudendal nerves transected bilaterally via a dorsal incision in order to denervate the external urethral sphincter. In the collagen and MDSC groups (C & M), injection of collagen or MDSC was made into the proximal urethra after pudendal nerve transection. At 4 and 12 week, visually identified LPP and CP measurements were made using the vertical tilt/intravesical pressure clamp model of stress urinary incontinence. The rats were then sacrificed and urethra harvested for histology. Both LPP and CP were significantly lower in the denervated (D) group at each time compared with the normal (N), C, and M groups, and both LPP and CP in the C and M groups were significantly higher than in the D group at both 4 and 12 weeks. The persistence of MDSC over the period of study was verified by histology. Thus pudendal nerve denervation led to a progressive decline in LPP and CP that was evident at 4 week and persisted to 12 week, and injection of MDSC into the denervated rats led to a long term increase in LPP and CP.