Urologic Diseases Research Updates
NIDDK-funded Scientists Successfully Implant Urethras Grown from Boys’ Own Cells
Researchers at Wake Forest University’s Institute for Regenerative Medicine have successfully implanted lab-grown urethras in five boys who suffered pelvic trauma. The scientists constructed urethras from muscle and epithelial cells taken from the boys’ own bladders. All five implanted urethras were still functioning 3 to 6 years after implantation.
“Tissue engineered urethras, created with patients’ own cells, can be used to successfully treat complex urethral defects,” reported Anthony Atala, M.D., director of Wake Forest University’s Institute for Regenerative Medicine, and co-authors, April 2, 2011, in The Lancet. “The tubularized engineered urethras showed histological and functional characteristics similar to native urethras and maintained adequate outflow for up to 6 years.” Doctors often use tissues grafted from the cheek or other skin areas to repair urethral defects. However, complex repairs, such as those caused by trauma, often require shaping tissue grafts into a tube. Tubularized tissue grafts, however, have a high failure rate. Over time they can become narrow and block urine.
Based on a similar technique Atala’s team developed to grow bladders, the scientists made tubularized mesh scaffolds out of a biodegradable suturing material called polyglycolic acid. They then coated the insides of the scaffolds with cultured uroepithelial cells. The outsides of the scaffolds were coated with cultured muscle cells. The coated scaffolds were then incubated in the lab for several weeks while the cells adhered and formed solid tissues. Construction of each urethra took 4 to 7 weeks.
When completed, the lab-grown urethras, which were sized according to the patients’ needs, ranged from 4 to 6 centimeters long. Surgeons then replaced each boy’s damaged section of urethra with lab-grown urethra. A urinary catheter was needed for 2 to 4 weeks after surgery until the new connections healed and the implant developed blood vessels.
Studies conducted after urinary catheter removal showed the boys achieved a normal urinary flow rate. Based on post-surgical biopsies, “the engineered urethras appeared to have a normal architecture by 3 months after implantation,” according to the report. “There were no aberrant histological changes over time.”
Surveys completed by the boys and their parents indicated satisfaction with the procedure. At last follow-up, all boys were continent.
“We have shown that urethral structures can be engineered and remain functional in a clinical setting in the long term,” wrote the authors, whose technique is the first to successfully use patients’ own cells to build tailor-made urethras. Wake Forest University’s Institute for Regenerative Medicine has thus far developed 22 types of lab-grown tissues, including blood vessels, ears, and digits. For more information about the Institute for Regenerative Medicine, visit www.wakehealth.edu/wfirm.
The research was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
The National Kidney and Urologic Diseases Information Clearinghouse, part of the NIDDK, has information about urologic diseases. For more information, visit www.urologic.niddk.nih.gov.
NIH Publication No. 11–5743