Patients receive tailor-made urethras grown in a lab from their own cells
In a move that augurs well for the engineering of replacement tissues and organs, researchers have reported the world's first successful implantation of urinary tubes grown in the laboratory using the patients' own cells. Between March 2004 and July 2007, the research team from the Institute for Regenerative Medicine at Wake Forest University Baptist Medical Center and colleagues engineered urinary tubes, or urethras, for five boys aged 10 to 14 using cells from the boys' own bladders to replace damaged segments. Tests showed the engineered tissue remained functional throughout the median six-year follow-up period.
Defective urethras can be the result of injury, disease or birth defects. While short defects in the tube are often easily repairable, larger defects can require a tissue graft, usually taken from skin or from the lining of the cheek. However, these grafts can have failure rates of more than 50 percent, often becoming narrowed, which leads to infections, difficulty urinating, pain and bleeding.
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The tailor-made urethras built be the researchers were engineered by taking a small one-half inch by one-half inch bladder biopsy from each patient, from which the scientists isolated smooth muscle cells and endothelial cells – the cells that line blood vessels and other tubular structures. The scientists then multiplied these cells in the lab for six weeks before placing them on a three-dimensional scaffold shaped like a urethral tube and sized for each individual patient.
The smooth muscle cells were placed on the outside and the endothelial cells placed on the inside of the scaffolds, which were made of a biodegradable mesh material. The scaffolds were then incubated for seven days, with all surface areas completely covered in cells by day six. The total time for construction of the replacement urethras ranged from four to seven weeks.
After incubation, the replacement tubes were surgically implanted with the defective segment of the urethra and scar tissue removed from the patients and the replacement tubes sewn in place inside the body, where the cells continued to expand and tissue formation began. Three months after implantation, biopsies showed that the engineered urethras had normal layers of epithelial and smooth muscle. Flow measurements, urine tests and patient questionnaires confirmed the lack of common symptoms resulting from the narrowing of urethral tubes, such as nighttime leaking, straining to urinate and urinary tract infections.
"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, M.D., a pediatric urologic surgeon, director of the Wake Forest Institute for Regenerative Medicine and author of the study published online at The Lancet. "This is an example of how the strategies of tissue engineering can be applied to multiple tissues and organs."
The approach used by Atala's team is similar to that used to engineer replacement bladders that were implanted in nine children from 1998, becoming the first in the world to implant laboratory-grown organs in humans. Similar scaffolding techniques have also been used to stimulate bone and cartilage growth in joints. Researchers at the Institute for Regenerative Medicine at Wake Forest University Baptist Medical Center are currently working to engineer more than 30 different replacement tissues and organs.