Engraftment of Transplanted Buccal Epithelial Cells onto the Urethrotomy Site, Proven Immunohistochemically in Rabbit Model; a Feat to Prevent Urethral Stricture Recurrence

Horiguchi, Akio; Shinchi, Masayuki; Ojima, Kenichiro; Hirano, Yusuke; Kubota, Toshihiro; Mayumi, Yoshine; Miyai, Kosuke; Miura, Ichiro; Iwasaki, Masanori; Vaddi, Suryaprakash; Senthilkumar, Rajappa; Preethy, Senthilkumar; Katoh, Shojiro; Abraham, Samuel JK

doi:10.1007/s12015-022-10466-1

Cited by 6 publications

(11 citation statements)

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“…The procedure was successful in four of six patients, yielding more than a 3-year recurrence-free interval. The subsequent use of this method in a rabbit model confirmed the success of buccal mucosal epithelial cell transplantation [ 109 , 110 ]. Recently, Scott et al [ 107 ] proposed a novel method of urethral stricture treatment using liquid buccal mucosal grafts to augment direct vision internal urethrotomy.…”

Section: Clinical Studiesmentioning

confidence: 81%

Cell-Based Therapy for Urethral Regeneration: A Narrative Review and Future Perspectives

Jin,

Zhao,

Yang

et al. 2023

Biomedicines

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Urethral stricture is a common urological disease that seriously affects quality of life. Urethroplasty with grafts is the primary treatment, but the autografts used in clinical practice have unavoidable disadvantages, which have contributed to the development of urethral tissue engineering. Using various types of seed cells in combination with biomaterials to construct a tissue-engineered urethra provides a new treatment method to repair long-segment urethral strictures. To date, various cell types have been explored and applied in the field of urethral regeneration. However, no optimal strategy for the source, selection, and application conditions of the cells is available. This review systematically summarizes the use of various cell types in urethral regeneration and their characteristics in recent years and discusses possible future directions of cell-based therapies.

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Section: Clinical Studiesmentioning

confidence: 81%

Cell-Based Therapy for Urethral Regeneration: A Narrative Review and Future Perspectives

Jin,

Zhao,

Yang

et al. 2023

Biomedicines

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“…Shinichi et al have reported a study in which an insulin-like growth factor 1 sustained-release collagen urethral catheter significantly improved wound healing and prevented urethral stricture after urethral injury [12]. We have already reported the success of the BEES-HAUS procedure in clinical and animal studies of urethral stricture [7,8]. The rationale to use a combination of 2D and 3D-TGP cells for transplantation was to utilize the maximum quantity of cells that can be cultured in vitro as increased cell counts have been reported to increase the success of engraftment and repair [13].…”

Section: Discussionmentioning

confidence: 99%

“…A 6-month urethroscopy revealed healthy mucosa at the urethrotomy site. In a subsequent animal study in rabbits, we demonstrated the proof of engraftment of transplanted buccal mucosal cells in BEES-HAUS over the urothelium at the urethrotomy site by immunohistochemistry markers positive for buccal epithelium, while negative for urothelium [8]. In this BEES-HAUS procedure, we utilized a combination of twodimensional (2D) monolayer cultured cells and the three-dimensional (3D) TGP cultured cells that were transplanted using the TGP as a carrier [7][8][9] (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

A hybrid combination of in vitro cultured buccal mucosal cells using two different methodologies, complementing each other in successfully repairing a stricture-inflicted human male urethral epithelium

Horiguchi,

Kushibiki,

Yoshine

et al. 2023

Preprint

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BackgroundAutologous buccal mucosal tissue derived cell transplantation techniques in repairing a stricture inflicted male urethral epithelium have been evolving. There was not much of clarity on the cell type, in vitro culture methods and the mode of transplantation, until we reported our buccal epithelium expanded and encapsulated in scaffold-hybrid approach to urethral stricture (BEES-HAUS) clinical study yielding a successful engraftment and repair with a long-term patency. We herein report with technical clarity on the advantages of mixing two-dimensional (2D) monolayer cultured fibroblast like cells and three dimensional (3D) thermo-reversible gelation polymer (TGP) cultured cells; the former secreting IGF-1, a cytokine known for its healing effects and the latter expressing epithelial surface markers in flow cytometry, both sourced from human buccal tissue, together transplanted using TGP as a carrier.MethodsHuman buccal tissues (n=22) redundant after urethroplasty surgery was used after informed consent and IEC approval. They were enzyme digested, divided into two portions; one was cultured as monolayer method (2D) and the other in 3D in TGP. Flowcytometry and quantification of IGF-1 in cell culture supernatant through the culture period were undertaken.ResultsIn flowcytometry, the cells on day 0, lacked AE1/AE3 - pancytokeratin expression indicative of epithelial phenotype of culture, which progressively increased in the 3D-TGP group, during invitro culture of up to 21 days. The 2D showed expression of only fibroblasts like cells that were negative for AE1/AE3 but positive for CD140b. IGF-1 secretion was significantly higher in 2D cultures than in 3D-TGP (p-value < 0.05).ConclusionThe 3D- TGP cultured cells of epithelial nature and the 2D cultured fibroblast like cells secreting IGF-1, together when transplanted using TGP scaffold as a carrier, adapted to a hostile in vivo milieu after releasing the fibrous strands with urethrotomy, successfully engrafted and repaired a stricture-inflicted male urethral epithelium in the BEES-HAUS procedure. While this hybrid combination of cells are considered to have potential in managing other epithelial damages, further research of such hybrid combination and their behaviour in disease affected environments may help to expand this solution in regenerating and repairing other tissues and organs as well.Graphical abstractIllustration of pathogenesis of urethral stricture and the contribution of the hybrid combination of two-dimensional (2D) and three dimensional, 3D-TGP (Thermo-reversible gelation polymer) cultured cells to the successful repair of the stricture-inflicted male urethral epithelium in the buccal epithelium expanded and encapsulated in scaffold-hybrid approach to urethral stricture (BEES-HAUS) technique.

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“…However, myofibroblast conversion is a double-edged sword as the underlying hurdle of over-proliferation is a major issue, especially related to malignant transformation as well as fibrosis leading to urinary obstruction [3,7,8]. Earlier, myofibroblast over-proliferation was reported as the key pathological mechanism of urethral stricture in men [9] which has been postulated to be potentially addressed by controlled myofibroblast proliferation using techniques such as cell therapies that involve TGF-beta, IGF release scaffolds, BEES-HAUS [10][11][12][13][14], etc. Therefore, in-depth exploration of cell therapies is critical to improving the efficacy and standardization of these therapies for SUI-especially in characterizing different types of cells used in therapeutic applications, their specific contribution to the process of healing such as factors or cytokines produced by each cell type, validation of such outcomes in relevant basic and translational studies pertaining to the optimal proliferation of myofibroblasts in the case of SUI.…”

mentioning

confidence: 99%

Editorial

2022

JSRM

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Engraftment of Transplanted Buccal Epithelial Cells onto the Urethrotomy Site, Proven Immunohistochemically in Rabbit Model; a Feat to Prevent Urethral Stricture Recurrence

Abstract: Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Cited by 6 publications

References 4 publications

Cell-Based Therapy for Urethral Regeneration: A Narrative Review and Future Perspectives

Cell-Based Therapy for Urethral Regeneration: A Narrative Review and Future Perspectives

A hybrid combination of in vitro cultured buccal mucosal cells using two different methodologies, complementing each other in successfully repairing a stricture-inflicted human male urethral epithelium

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