Stem cells used to grow new bladders in rats

Montreal-Adipose-derived stem cells (ADSCs) can be coaxed into restoring urethral function and even building new bladders in an animal model, UCLA researchers report, providing hope that one day a similar approach can be used for the treatment of stress urinary incontinence and even bladder reconstruction in humans. Human trials, however, are still a long way off.

Dr. Rodriguez presented the results of her group's study here at the International Continence Society annual meeting.

Injecting these cells into the urethras of a rat model of stress incontinence, in which female rats had atrophic urethras, revealed that these cells remained viable for up to 12 weeks. Urodynamic assessment of the rats demonstrated that the injected ADSCs also restored urethral resistance.

"There is evidence that there is an effect of [human] incontinence that is due to smooth muscle loss," Dr. Rodriguez said. "There is evidence that with aging there is atrophy of the smooth muscle bundles as there is of the skeletal muscle. I think there is definitely evidence that about 30% or 40% of the continence mechanism might be due to [loss of function of] the smooth muscle and the intrinsic function of the urethra."

A procedure that restores smooth muscle function in the urethra, therefore, has potential for the treatment of stress incontinence in humans.

Even more exciting is the investigators' work in actually engineering new bladders in cystectomized rats using ADSCs. They performed a partial cystectomy in 45 rats. Fifteen of these animals then underwent bladder augmentation with a polylactide-co-glycolide (PLGA) graft. Another 15 underwent bladder augmentation with a 1 cm² patch of bladder engineered by ADSC-derived smooth muscle cells. The final 15 served as a control group and underwent no treatment.

Urodynamic studies revealed that the bladders rebuilt with the ADSCs had capacity and compliance superior to the partial cystectomy bladders. Histologic analysis demonstrated that the ADSC bladders, unlike the PLGA bladders, also showed development of smooth muscle layers similar to those seen in normal, healthy bladders. Finally, isometric studies revealed improved contractility among the bladders augmented with ADSC-derived smooth muscle cells.

"ADSCs are an abundant source of pluripotent cells that can provide functional smooth muscle cells," Dr. Rodriguez said. "ADSC-derived smooth muscle cells can be used to restore urethral resistance in an animal model of SUI [and] can be used to engineer bladder tissues, which restore native bladder capacity and compliance. After 3 months' time, bioengineered bladder grafts have smooth muscle phenotype and functional response."

While these findings demonstrate an exiting proof of principle, Dr. Rodriguez said that it is still a long jump to human trials. Some hurdles yet to be crossed before human studies begin include improving the reliability of the procedure, determining whether the results can be maintained long-term, and ensuring that bladder stones do not develop in engineered bladders.

"I don't think the procedure would do humans any harm, but we have yet to determine if it will do them any good," she said.