Liquid buccal mucosa graft endoscopic urethroplasty: a validation animal study

Scott, Kathryn A.; Li, Guanqun; Manwaring, Jared; Nikolavsky, Daniela A; Fudym, Yelena; Caza, Tiffany; Badar, Zain; Taylor, N C; Bratslavsky, Gennady; Kotula, Leszek; Nikolavsky, Dmitriy

doi:10.1007/s00345-019-02840-5

Cited by 11 publications

(12 citation statements)

References 22 publications

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“…The techniques used to create strictures, which usually comprise electrocautery or other electro-coagulation methods, do not yield reproducible strictures and cause complications [ 11 , 12 ]. The other animal studies on similar lines have proven the engraftment of minced oral mucosal tissue [ 2 ] in strictured urethra but not free oral mucosal epithelial cells, to our knowledge. We followed the method reported by Shinchi et al.…”

Section: Discussionmentioning

confidence: 82%

“…The complication rate is 12.5%, especially during penile urethroplasty, and urinary fistula, graft contracture and graft failure are common hurdles [ 2 ]. Novel potential treatment options include regenerative approaches, especially cell therapy-based approaches [ 2 , 3 ]. Minced buccal mucosal graft urethroplasty has been earlier reported [ 2 ] in this regard.…”

Section: Introductionmentioning

confidence: 99%

“…Novel potential treatment options include regenerative approaches, especially cell therapy-based approaches [ 2 , 3 ]. Minced buccal mucosal graft urethroplasty has been earlier reported [ 2 ] in this regard. Vaddi et al.…”

Section: Introductionmentioning

confidence: 99%

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Successful engraftment of epithelial cells derived from autologous rabbit buccal mucosal tissue, encapsulated in a polymer scaffold in a rabbit model of a urethral stricture, transplanted using the transurethral approach

Horiguchi

Ojima

Shinchi

et al. 2021

Regenerative Therapy

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Background A pilot study reported an autologous buccal mucosal cell transplant in humans through the trans-urethral route using the buccal epithelium expanded and encapsulated in scaffold—hybrid approach to urethral stricture (BEES-HAUS), a minimally invasive approach to treat urethral stricture. Although successful outcomes were achieved in that study, for further validation, it is essential to prove that the transplanted buccal epithelium was engrafted over the urothelium through histological examination of the urethra, harvested post-transplant, which is infeasible in humans. Herein, we report the successful creation of an animal model of urethral stricture and the engraftment of epithelial cells derived from autologous buccal mucosal tissue, encapsulated in a thermo-reversible gelation polymer (TGP) scaffold, transplanted by trans-urethral route. Methods An animal model of urethral stricture was created in Japanese white male rabbits using electro-coagulation. Buccal tissue was harvested from the rabbits and subjected to enzyme digestion, followed by 5–7 days of in vitro culture in conventional two-dimensional (2D) culture and in a 3D platform of thermo-reversible gelation polymer (3D-TGP) culture. The cells harvested from the groups were mixed and encapsulated and transplanted with TGP, by transurethral catheterization. Fourteen days later, the urethra was harvested and subjected to histological examination. The buccal biopsy tissue, cells after digestion and cells post-culture were also subjected to histological examination. Urethrogram and endoscopy images were recorded at different time points. Results The stricture was successfully created, with the coagulated area markedly stenosed. Histological staining of the cells after in vitro processing showed that the cells grew with native epithelial and rounded cell morphology in 3D-TGP while they differentiated into fibroblast like-cells in 2D culture. Histological staining of the urethral tissue after transplantation revealed the engraftment of the transplanted buccal mucosal cells, with stratified squamous epithelium over the specialized stratified urothelium in the urethrotomy site. Conclusion We used histology to prove the successful engraftment of TGP-encapsulated buccal mucosal epithelial cells in an animal model of urethral injury with healing of the injured tissue. The model of urethral stricture and cell therapy, using a transurethral approach, recapitulates the previously reported BEES-HAUS approach and lays the foundation for larger multi-centric translational clinical studies.

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Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

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Successful engraftment of epithelial cells derived from autologous rabbit buccal mucosal tissue, encapsulated in a polymer scaffold in a rabbit model of a urethral stricture, transplanted using the transurethral approach

Horiguchi

Ojima

Shinchi

et al. 2021

Regenerative Therapy

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“…This injection decreases recurrence rates after DVIU in animal models and has been trialed in humans with promising but mixed results. 78 , 79 Also available are solid tissue constructs or scaffolds, potentially seeded with autologous cells, designed to simulate native urethral mucosa. 67 These grafts can be constructed from decellularized natural scaffolds (generally bladder, small intestine, or dermis) or fully synthetic polymers and then seeded with cells harvested from bladder biopsy, voided urine, or other sources.…”

Section: Alternative Graft Optionsmentioning

confidence: 99%

Recurrent Anterior Urethral Stricture: Challenges and Solutions

Mershon¹,

Baradaran²

2021

RRU

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Recurrent male anterior urethral stricture disease is a complex surgical challenge that should be managed by reconstructive urologists with experience in stricture management. Diagnosis of recurrence requires both anatomic narrowing and patient symptoms identified on validated questionnaires, with limited role for intervention in asymptomatic treatment "failures". Endoscopic management has a very specific role in recurrence, and the choice of technique for urethroplasty depends on pre-operative urethrography and cystoscopy. Surgical success depends on addressing patient concerns, complete stricture excision, tissue quality optimization, and the use of multi-stage repair when indicated. Augmentation with genital skin flaps and/or grafts is often required, with buccal mucosa as the ideal graft source if local tissue is compromised. Salvage options including urinary diversion and perineal urethrostomy must also be considered in debilitated patients with severe disease or repeated treatment failures. Unique patient populations including patients with hypospadias and lichen sclerosis are among the highest risk for repeated recurrence and require special care in surgical technique, graft selection, and post-operative management.

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“…With a similar aim of developing a better mucosal replacement for urethral reconstruction, Pusateri and colleagues performed a pilot study with placental membrane grafts for rabbit urethral reconstruction with impressive results [9]. Finally, Scott and associates shared results of a validation study in a rabbit stricture model utilizing liquid buccal mucosal graft for endoscopic treatment of anterior urethral strictures [10].…”

mentioning

confidence: 99%