Neo-bladder Constructs for Children With Spina Bifida

A recent achievement in the emerging field of regenerative medicine is implantation of autologous neo-bladder constructs on neurogenic bladders in pediatric patients with spina bifida. The implanted constructs promote tissue regeneration, increasing bladder capacity and compliance. “The neo-bladder can potentially reduce the risks associated with augmentation enterocystoplasty for failing bladders,” says UAB pediatric urologic surgeon David B. Joseph, MD.

Approximately 95% of children born with myelomeningocele, the neural tube defect known as spina bifida, have neurogenic bladder. Dysfunction includes urinary incontinence, urinary tract infection, and upper tract deterioration leading to high intravesical pressure and reduced bladder capacity. Resulting hydronephrosis or vesicoureteral reflux damages kidneys and can result in end-stage renal disease.

Current medical treatment includes anticholinergic medications and clean intermittent catheterization every 3 to 4 hours. For the 20% of patients refractory to such approaches, augmentation enterocystoplasty, in which a segment of the terminal ileum is used to increase bladder size, is the most commonly performed procedure. The surgery, however, has substantial short- and long-term risks: postoperative ileus, peritonitis, intussusception, obstruction, and secretion of mucus that may cause stone formation, worsen urine viscosity requiring bladder irrigations and catheterization, and increase infections. A potential risk for malignant disease also exists. “In light of such risks, alternative ways to increase bladder capacity and compliance are desperately needed,” Joseph says.

Regenerative Bladder Construct
The neo-bladder relies on technology developed by researchers at Children’s Hospital Boston and Tengion, which specializes in regenerative medicine. Scientists propagate autologous urothelial cells and smooth muscles cells ex vivo for about 6 weeks. They seed the new cohort of cells onto a grapefruit-sized polyglycolide and polylactide dome that surgeons suture to native bladder. To enhance vascularization, surgeons mobilize and wrap omentum from the patient’s abdomen around the newly constructed organ.

In a pilot study by pioneer researcher Anthony Atala et al, the bladder construct improved urodynamics and eliminated morbidity associated with augmentation enterocystoplasty (Lancet. 2006;367:1241-1246).

Two phase 2 trials are underway: One in adult patients with spinal cord injury, and one in a pediatric population. Joseph, principal investigator for the pediatric trial, and colleagues at three other sites implanted neo-bladder constructs in 10 children with neurogenic bladders secondary to spina bifida. “The operative phase of the study is complete. Postoperative assessment will include urodynamic measurements of bladder compliance, capacity, and overactivity. We are eagerly awaiting those results,” Joseph says. “A successful outcome will eliminate mucus production, minimizing risk for stone formation, urinary infection, and the late complication of tumor development.” Investigators will continue to assess risks compared with those of the standard-of-care procedure and, based on feedback from the US Food and Drug Administration, plan to open a phase 3 trial in late 2008.

For more information:
Dr. David Joseph
1.800.UAB.MIST
mist@uabmc.edu