Laurie Barclay, MD

April 3, 2006 — Investigators successfully grew and implanted tissue-engineered autologous bladders into 7 patients needing cystoplasty, according to a report in the April 4 issue of The Lancet. However, more study is required before use of the procedure becomes widespread.

"Patients with end-stage bladder disease can be treated with cystoplasty using gastrointestinal segments," write Anthony Atala, from Wake Forest University School of Medicine in Winston-Salem, North Carolina, and colleagues. "Engineering bladder tissue with selective cell transplantation might provide a means to create functional new tissues. Cell-based approaches to engineering bladder tissue have been reported, and bioengineering has allowed creation of functional neo-bladder tissues in several animal models."

Seven patients aged 4 to 19 years, with myelomeningocele and high-pressure or poorly compliant bladders, were identified as candidates for cystoplasty. Each patient underwent bladder biopsy, and urothelial and muscle cells were grown in culture and seeded on a biodegradable bladder-shaped scaffold made of collagen, or on a composite of collagen and polyglycolic acid. About 7 weeks later, the autologous engineered bladder constructs were used for reconstruction, and implanted either with or without an omental wrap. After implantation, patients underwent serial urodynamics, cystograms, ultrasounds, bladder biopsies, and serum analyses.

Mean follow-up time was 46 months (range, 22-61 months). The composite engineered bladders with an omental wrap had the greatest postoperative mean bladder leak point pressure decrease (56%), volume increase (1.58-fold) and compliance increase (2.79-fold). Bowel function returned promptly after surgery. There were no metabolic consequences or urinary calculi detected; mucus production was normal; and renal function was preserved. Biopsies of the engineered bladders showed an adequate structural architecture and phenotype.

"Engineered bladder tissues, created with autologous cells seeded on collagen-polyglycolic acid scaffolds, and wrapped in omentum after implantation, can be used in patients who need cystoplasty," the authors write. "The urodynamic results were similar to those that would be expected with the use of gastrointestinal tissue. However, the patients did not experience any of the ill effects associated with gastrointestinal tissues."

As in patients undergoing cystoplasty with bowel segments, these patients continued to need intermittent catheterization.

"The implanted composite engineered bladders showed improved functional parameters that were durable over a period of years," the authors conclude. "Although follow-up of longer than 5 years is reported, additional studies will be needed before this procedure can be used widely."

The authors note that several patents relating to the technology described in this article were assigned to Children's Hospital and were licensed to Tengion in 2003. Five authors report various financial relationships with Tengion.

In an accompanying editorial, Steve Y. Chung, from the Advanced Urology Institute of Illinois in Spring Valley, notes that vascular supply and neural restoration of the engineered bladders needs further study.

"Atala and colleagues should be praised for the milestone they have reached, but further multi-institutional studies are needed with longer follow-up," Dr. Chung writes. "Until then, intestinal cystoplasty remains the gold standard."

Dr. Chung reports no relevant financial relationships.

Lancet. Published online April 4, 2006.

Reviewed by Gary D. Vogin, MD