Laboratory-grown urethras successfully implanted in young patients

Researchers at the Institute for Regenerative Medicine have used patients’ own cells to build tailor-made urethras and successfully replace damaged tissue.

In a study published online in The Lancet (March 7, 2011), the researchers report replacing damaged segments of urethras in five boys. Tests to measure urine flow and tube diameter showed that the engineered tissue remained functional throughout the 6-year follow-up period.

"These findings suggest that engineered urethras can be used successfully in patients and may be an alternative to the current treatment, which has a high failure rate," said senior author Anthony Atala, MD, of the Institute for Regenerative Medicine at Wake Forest University Baptist Medical Center, Winston-Salem, NC. "This is an example of how the strategies of tissue engineering can be applied to multiple tissues and organs."

Between March 2004 and July 2007, the team built engineered urethras for five boys, ages 10 to 14 years, using the patients’ own cells. Three patients had widespread injury due to pelvic trauma and two patients had previous urethra repairs that had failed. The engineered tubes were used to replace entire segments of damaged urethra in the posterior section. The children in the study were treated at the Federico Gomez Children’s Hospital in Mexico City.

The first step in engineering the replacement urethral segments was taking a small bladder biopsy from each patient. Smooth muscle cells and endothelial cells were multiplied in the lab for 3 to 6 weeks and were then placed on a three-dimensional scaffold shaped like a urethral tube. Smooth muscle cells were placed on the outside of the scaffold and endothelial cells on the inside. After cell placement, the scaffolds were incubated for 7 days, with the total time for construction ranging from 4 to 7 weeks. By day six, all surface areas were completely covered with cells.

After incubation, the tubes were surgically implanted by removing the defective segment of the urethra and scar tissue and sewing the replacement tubes in place. Once in the body, the cells continued to expand and tissue formation began.

Biopsies showed that the engineered urethras had normal layers of epithelial and smooth muscle within 3 months after implantation. Flow measurements, urine tests, and patient questionnaires confirmed patient satisfaction as measured by lack of nighttime leaking, straining to urinate, and urinary tract infections.