Treatment for chronic ischaemia-induced bladder detrusor dysfunction using bone marrow mesenchymal stem cells: an experimental study.

The mechanism of ischaemia-induced bladder dysfunction is not entirely clear, but is thought to be a result of the ischaemia-related M-receptor hypersensitivity to acetylcholine. In addition to nerve injury, ischaemia may cause bladder detrusor fibrosis and urethra de-epithelialization. Bladder dysfunctions caused by bladder outlet obstruction (BOO) and aging detrusor were considered to be associated with chronic ischaemia. To date, there has been no effective treatment for the histological and functional changes of the bladder caused by bladder ischaemia. The present study evaluated the feasibility and effectiveness of using bone marrow mesenchymal stem cells in the treatment of chronic ischaemia-induced bladder detrusor dysfunction in an experimental model. Bone marrow mesenchymal stem cells from Sprague-Dawley (SD) rats were injected into the common iliac artery of experimental animals, then bilateral iliac arteries were ligated and doxazosin mesylate was intragastrically administered. Eight weeks later, urodynamic examination and intravesical pressure measurements were performed on experimental animals. Histological changes of the taken bladder from sacrificed SD rats were evaluated by immunohistochemistry and trichrome staining and the images captured were analyzed by a software program. The average intravesical pressure and detrusor contraction power of the ischaemia group was 16.21±5.26 and 17.26±5.72; those of the experimental group were 24.02±10.06 and 25.84±11.99; the average intravesical pressure and detrusor contraction power of the control group was 28.56±4.48 and 29.57±5.01. The average intravesical pressure and detrusor contraction power of the ischaemia group were significantly lower than those of the experimental and control group, while no significant difference was shown between the experimental and control groups. 5-Bromo-2'-deoxyuridine (BrdU) staining for the experimental group was positive. The percentage of the smooth muscle content in the bladder wall was (25.21±6.28)%, (49.38±6.32)% and (48.00±17.39)% for ischaemia, experimental and control group, respectively. The percentage of smooth muscle in the bladder wall of the ischaemia group was significantly lower than that of the experimental and control group, while no significant difference was observed between the experimental and control groups. The number of nerve fibers per high power field of the experimental group was significantly higher than that of the ischaemia group, but lower than the control group. In conclusion, the percentage of smooth muscle content and the number of nerve cells per high power field decreases in ischaemia bladder, with detrusor contractility decreased. Injection of stem cell suspension into the common iliac artery in rats with ischaemic bladder, followed by intragastric administration of doxazosin mesylate, makes transplanted stem cells regenerate in the bladder tissue, increases the percentage of smooth muscle content and nerve cells per high power field in the bladder wall, and improve bladder detrusor contraction function.