Periurethral cellular injection: Comparison of muscle-derived progenitor cells and fibroblasts with regard to efficacy and tissue contractility in an animal model of stress urinary incontinence

Abstract

Objectives. To compare muscle-derived cells (MDCs) and fibroblasts with regard to their potential for restoration of urethral function on injection in a previously established animal model of stress urinary incontinence. Methods. The animals were divided into four (dosage) or five (cell concentration) experimental groups: normal, nontreated controls (normal group) or bilateral sciatic nerve transection with either periurethral injection of saline (saline group), MDCs (MDC group), fibroblasts (fibroblast group), or MDC/fibroblast mixture (mixed group). At 4 weeks after injection, the leak point pressure (LPP) was measured and contractility testing and histologic analysis were performed. Results. The histologic examination demonstrated muscular atrophy in the saline group and new striated muscle fibers at the sites of MDC injection in the MDC group, but not in the fibroblast group. Denervation of the urethra resulted in a significant decrease of maximal fast-twitch muscle contraction amplitude to only 9% of normal. MDC injection into the denervated urethra significantly improved the fast-twitch muscle contraction amplitude to 73% of normal. The LPP of the normal, saline, MDC, fibroblast, and mixed groups at 4 weeks after treatment was 43.3 +/- 2.5, 25.8 +/- 1.4, 38.2 +/- 4.2, 38.3 +/- 1.2, and 34.5 +/- 3.3 cm H2O, respectively. In the cell dosage experiment, the LPP increased with increases in the injected cell number. Evidence of obstruction was observed in the high-dose (11 x 10(7) cells) fibroblast group. Conclusions. Although both MDCs and fibroblast injection increased the LPP in a stress urinary incontinence rat model, only MDCs significantly improved urethral muscle strip contractility. Moreover, urinary retention developed with high-dose fibroblast injection, but not with MDC injection.