A pioneering study has shown that tissue-engineered urethras, made with the boys' own cells, are functional and viable and show the characteristics of 'regular' urethras within 3 months. Such grafts can last at least six years, concludes the Article published Online First by The Lancet. The study is by Professor Anthony Atala, Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA, and colleagues; the work was funded by the US National Institutes of Health.
Complex urethral problems can be caused by injury, which can lead to an inability to urinate. Some patients with urethral strictures (narrowing) repeatedly have infections, experience straining and major discomfort, and have blood in their urine. Present methods of urethral reconstruction, with tissue grafts (eg, skin), have shown that on-lay repairs often have better outcomes than tubularised repairs. Tubularised tissue grafts might be needed for complex or long urethral defects, but have a high proportion of failures. There has been no previous work done in terms of creating tubularised engineered urethras for patients, which could be used instead of grafts.
Five boys who had urethral defects were included in the study. A tissue biopsy was taken from each patient's bladder/urethral area, and the muscle and epithelial cells were expanded and seeded onto tubularised scaffolds. Patients then underwent urethral reconstruction with the tissue-engineered tubularised urethras. A number of tests, including urine flow and biopsies, were completed several times during the follow-up
The five boys (aged 10-14 years) had surgery between 2004 and 2007, with follow-up (median 71 months) completed in mid 2010. Biopsies confirmed the presence of both epithelial and muscle cells in the reconstructed urethras. All five boys were continent at the end of follow up, with a median end maximum urinary flow rate was 27•1 mL/s. The reconstructed grafts had developed a normal appearing architecture by 3 months after implantation.
The engineered tubes were used to replace entire segments of damaged urethra in the section that runs between the penis and the prostate (posterior section) -- considered the most difficult to repair. The authors note that additional studies will be required to assess the technique in adult patients, and to assess whether the technique works on other parts of the urethra.
They conclude: "All five boys were continent at last follow-up…Tissue engineered urethras, created with patients' own cells, can be used to successfully treat complex urethral defects. The tubularised engineered urethras showed histological and functional characteristics similar to native urethras and maintained an adequate outflow for up to 6 years. Tissue engineered urethras could be a new alternative source for reconstruction."
In a linked Comment, Dr Karl-Dietrich Sievert, Department of Urology, University of Tuebingen, Germany, says that it needs to be shown that these reconstructed urethras are cost-effective, in terms of actual tube length, in a wider indication in a larger group of patients, and says the results must now be followed up with a multi-institutional trial.
For Professor Anthony Atala, Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA, please contact Karen Richardson in Media Relations. T) +1 336-716-4453 E) krchrdsn@wfubmc.edu
Dr Karl-Dietrich Sievert, Department of Urology, University of Tuebingen, Germany. T) +49 7071 2980349 E ) Karl.Sievert@med.uni-tuebingen.de
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Journal
The Lancet