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Year : 2012  |  Volume : 28  |  Issue : 4  |  Page : 470-471
 

Tissue-engineered autologous urethras for complex urethral problems: From envision to reality


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Date of Web Publication10-Jan-2013

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How to cite this article:
Pradhan MR. Tissue-engineered autologous urethras for complex urethral problems: From envision to reality. Indian J Urol 2012;28:470-1

How to cite this URL:
Pradhan MR. Tissue-engineered autologous urethras for complex urethral problems: From envision to reality. Indian J Urol [serial online] 2012 [cited 2019 Jun 27];28:470-1. Available from: http://www.indianjurol.com/text.asp?2012/28/4/470/105803

Raya-Rivera A, Esquiliano DR, Yoo JJ, Lopez-Bayghen E, Soker S, Atala A. Tissue-engineered autologous urethras for patients who need reconstruction: an observational study. Lancet 2011;377:1175-82.



   Summary Top


Application of tissue engineering and regenerative medicine in urological practice has been recognized since the early 1990s and numerous in vitro and animal studies have been reported in the literature. In the cited study, Raya-Rivera et al., have reported the use of engineered tubularized urethras from autologous urothelial tissue for reconstruction of complex posterior urethral defects in humans. The study included five young patients in the age range of 10-14 years with posterior urethral defects; three patients with a complete posterior urethral disruption caused by pelvic trauma and two patients with history of failed substitution urethroplasty. The median length of urethral defect was 5 cm (range 4-6 cm). Autologous urothelial tissue (1x1 cm) was harvested by suprapubic open-bladder biopsy. The smooth muscle and urothelial cells were isolated and expanded separately in tissue culture media. The epithelial cells were seeded onto the luminal surface and muscle cells onto the outer surface of a biodegradable scaffold prepared from tubularized mesh of polyglycolic acid (PGA). The seeded scaffolds were further incubated for seven more days in tissue culture media. Construction of the neo-urethras took four to seven weeks of time. The tubularized engineered urethral constructs were surgically implanted using absorbable sutures. Urethral catheter was removed four weeks after surgery. Patients were followed up with periodical uroflow measurements, cystourethroscopy, cystourethrography and serial endoscopic cup biopsies for a median of 71 months (range 36-76 months). All the patients voided well with mean maximum flow rate of 25.1 ml/s and maintained wide urethral caliber with no stricture or diverticulum. Serial urethral biopsies showed that the engineered grafts had developed a normal-appearing architecture by three months after implantation with distinguishable layers of epithelia and smooth muscle. There were no aberrant histological changes over time.


   Discussion Top


The majority of urethral strictures are managed by anastomotic or onlay substitution urethroplasty. However, patients with long urethral defects or unhealthy urethral bed like in lichen sclerosus or with history of previous failed substitution repairs are difficult to manage. Buccal mucosal cell-seeded matrices have been used as on-lay grafts for urethral disease in patients with lichen sclerosus. [1] In graft repairs of the urethra, a portion of the native urethra is left in situ which often results in stricture recurrence. So complete replacement of the diseased urethra by healthy tissue is always desirable. Use of tubularized tissue grafts have been associated with disappointing results. [2] Engineered urethral tubes can be of immense help in these patients. Inspired by the success of their previous study reported in rabbits, the authors replicated the same in human subjects with favorable results. [3] The same authors have also published a clinical trial of engineered human bladder tissues in young patients with end-stage bladder disease. [4] It included seven young patients (age range 4-19 years) with myelomeningocele with high-pressure and poorly compliant bladders who were candidates for augmentation cystoplasty. They isolated autologous bladder urothelial and muscle cells, expanded the cells in vitro and attached them to various biodegradable bladder-shaped scaffolds made of collagen or collagen PGA composite. The resulting tissues were implanted into patients with or without omental wrapping. Patients showed clinical improvement with follow-up of 22-61 months (mean 46 months) and bladder biopsies revealed adequate structural architecture and phenotype. So from animal experimental studies, regenerative medicine and tissue engineering has made its way to human clinical use.

With increased use of engineered tissue products in animals and humans, certain queries are evolving. [5] Neuronal innervations of the engineered tissue and establishment of adequate vascular supply to the implanted organ are of major concern. Since it's difficult for organs to depend solely on diffusion for the delivery of nutrients and removal of waste products, better methods should be devised to establish adequate vascular supply to the implanted organs. Also, due to altered neurovascular supply, the response of these organs to various disease processes is to be studied in terms of pathology and clinical manifestation.

The present study being an experimental one, consists of a small number of patients from a particular age group and does not address the above mentioned queries. However, this technique has great potential for treatment of complex urethral diseases, both congenital and acquired. It has laid a strong foundation for further clinical research and larger studies with longer follow-up are necessary before engineered tissues can be employed in routine clinical use in humans. It will also stimulate further clinical studies involving other organs like the kidney, urethral sphincter and various endocrine and exocrine glands.

 
   References Top

1.Bhargava S, Patterson JM, Inman RD, MacNeil S, Chapple CR. Tissue-engineered buccal mucosa urethroplasty-clinical outcomes. Eur Urol 2008;53:1263-9.  Back to cited text no. 1
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2.Pansadoro V, Emiliozzi P. Which urethroplasty for which results? Curr Opin Urol 2002;12:223-7.  Back to cited text no. 2
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3.De Filippo RE, Yoo JJ, Atala A. Urethral replacement using cell seeded tubularized collagen matrices. J Urol 2002;168:1789-92.  Back to cited text no. 3
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4.Atala A, Bauer SB, Soker S, Yoo JJ, Retik AB. Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet 2006;367:1241-6.  Back to cited text no. 4
[PUBMED]    
5.Stanasel I, Mirzazadeh M, Smith JJ 3rd. Bladder tissue engineering. Urol Clin North Am. 2010;37:593-9.  Back to cited text no. 5
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