Regenerative Medicine Applied to Urethras

Urethras
2011 -- WAKE FOREST BAPTIST MEDICAL CENTER led a team of researchers that was the first in the world to successfully replace damaged tissue by using patients’ own cells to build tailor-made urethras in the lab. As reported in The Lancet, the research team replaced damaged sections of urethras in five children. Tests to measure urine flow and tube diameter showed that the engineered tissue remained functional throughout the six-year (median) 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
Anthony Atala, MD, senior author, chair of Urology and director of the Wake Forest Institute for Regenerative Medicine. “This is an example of how the strategies of tissue engineering can be applied to multiple tissues and organs.”

Atala’s team used a similar approach to engineer replacement bladders that were implanted in nine children beginning in 1999, becoming the first in the world to implant laboratory-grown organs in humans. Researchers at the institute are currently working to build replacement organs and develop therapies to promote healing from within for more than 30 different areas of the body.

Between March 2004 and July 2007, the research team built engineered urethras for five boys, ages 10 to 14, using the patients’ own cells. Three patients had widespread injury because of 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—considered the most difficult to repair. The children 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 (1/2” x 1/2”) bladder biopsy from each patient. From each sample, scientists isolated smooth muscle and endothelial cells and cultured them in the lab until having sufficient quantities for seeding on a three-dimensional, biodegradable scaffold shaped like a urethral tube. After cell placement, the scaffolds were incubated for seven days—with the total time for construction ranging from four to seven 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 three months after implantation. Flow measurements, urine tests and patient questionnaires confirmed patient satisfaction as measured by lack of leaking, straining to urinate and urinary tract infections—common symptoms when urethral tubes become narrowed.

The research was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases.Co-researchers were
James J. Yoo, MD, PhD, and Shay Soker, PhD, Wake Forest Baptist Medical Center, and Atlantida Raya-Rivera, Diego R. Esquiliano and Esther Bayghen, Metropolitan Autonomous University, Mexico.
Last Updated: 01-21-2014
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