Neurologic recovery and improved detrusor contractility using muscle-derived cells in rat model of unilateral pelvic nervetransection

Abstract

OBJECTIVES: To create a model of peripheral neuropathy and explore the potential of using muscle-derived cells (MDCs) to facilitate the regeneration of autonomic nerves and improve bladder function. Damage to the peripheral nerves that innervate the bladder from radical pelvic surgery is refractory to the currently available treatments. METHODS: Rat MDCs were isolated from the gastrocnemius muscle using the preplate technique. The unilateral pelvic nerve was cut in female Sprague-Dawley rats. Three experimental groups were included: control (n = 5); unilateral pelvic nerve transected with sham injection (n = 5); and unilateral pelvic nerve transected with injection of MDC (3 x 10(5) cells/site; n = 5). Two weeks after injection, the intravesical pressures were measured during electrical stimulation of the proximal transected preganglionic nerve. The contralateral major pelvic ganglion was excised to ensure that any observed bladder activity was due exclusively to inputs on the unilateral side. The rats were killed, the experimental side major pelvic ganglion was removed, and enkephalin immunoreactivity was counted. RESULTS: After unilateral pelvic nerve transection, no change occurred in bladder weight or capacity or postvoid residual urine volume. The maximal intravesical pressures for the control, sham, and MDC groups, after the contralateral pelvis had been cut, was 31.7 +/- 10.3, 9.6 +/- 4.5, and 15.2 +/- 7.7 cm H2O, respectively (P <0.05). After transecting the preganglionic pelvic nerve, the intensity of pericellular enkephalin immunoreactivity varicosities was significantly decreased in the sham group but unchanged in the MDC group compared with the control group. CONCLUSIONS: MDCs can promote peripheral autonomic nerve regeneration. The morphologic changes correlated with the functional neurologic recovery effect of MDCs. The underlying neurologic recovery mechanisms of MDCs need to be exploited.