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.
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.
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DOI：
10.1016/j.reth.2021.05.004
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发表时间：
2021-12
影响因子：
4.3
通讯作者：
Abraham SJ
中科院分区：
文献类型：
--
作者：
Horiguchi A;Ojima K;Shinchi M;Kushibiki T;Mayumi Y;Miyai K;Katoh S;Takeda M;Iwasaki M;Prakash VS;Balamurugan M;Rajmohan M;Preethy S;Abraham SJ
一项初步研究报道了人类自体颊粘膜细胞经尿道移植，使用扩展和包封的颊上皮支架混合入路治疗尿道狭窄（BEES-HAUS），这是一种微创治疗尿道狭窄的入路。虽然该研究取得了成功的结果，但为了进一步验证，有必要通过移植后采集的尿道组织学检查来证明移植的颊上皮是在尿路上皮上移植的，这在人类中是不可行的。在此，我们报告了成功建立尿道狭窄动物模型，并将来自自体颊粘膜组织的上皮细胞植入，包裹在热可逆凝胶化聚合物（TGP）支架中，经尿道途径移植。采用电凝法制备日本白兔尿道狭窄动物模型。取兔口腔组织进行酶消化，然后在常规二维（2D）培养和三维热可逆凝胶化聚合物（3D- tgp）培养中进行5-7天的体外培养。将各组细胞混合后包被TGP，经尿道置管移植。14天后，取尿道，行组织学检查。对口腔活检组织、消化后细胞和培养后细胞进行组织学检查。记录不同时间点的尿道造影和内窥镜图像。狭窄形成成功，凝固区明显狭窄。体外处理后的细胞组织学染色显示，3D-TGP培养的细胞具有天然上皮和圆形细胞形态，2D培养的细胞分化为成纤维细胞样细胞。移植后尿道组织的组织学染色显示移植的颊粘膜细胞植入，在尿道切开处的特化层状尿路上皮上有层状鳞状上皮。我们用组织学方法证实tgp包埋的颊粘膜上皮细胞成功植入尿道损伤动物模型，损伤组织愈合。采用经尿道入路的尿道狭窄和细胞治疗模型概括了先前报道的BEES-HAUS方法，并为更大的多中心转化临床研究奠定了基础。一种与人类尿道狭窄非常相似的动物模型可以被创造出来。包覆口腔粘膜上皮细胞的聚合物支架经尿道移植是可行的。移植细胞成功植入尿道切开术部位并愈合，在这类报道中首次得到证实。
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. 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. 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. 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. An animal model of urethral stricture that closely resembles that occurring in humans could be created. Trans-urethral transplantation of polymer scaffold encapsulated buccal mucosal epithelial cells could be accomplished. Successful engraftment of transplanted cells onto urethrotomy site with healing, proven in this first of its kind report.
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影响因子：
2.6
作者：
Shinchi, Masayuki;Kushibiki, Toshihiro;Horiguchi, Akio
通讯作者：
Horiguchi, Akio
影响因子：
2.6
作者：
Vaddi, Surya P.;Reddy, Vijaya B.;Abraham, Samuel J. K.
通讯作者：
Abraham, Samuel J. K.
影响因子：
11.1
作者：
Ram-Liebig G;Barbagli G;Heidenreich A;Fahlenkamp D;Romano G;Rebmann U;Standhaft D;van Ahlen H;Schakaki S;Balsmeyer U;Spiegler M;Knispel H
通讯作者：
Knispel H
影响因子：
3.1
作者：
Rao SK;Sudhakar J;Parikumar P;Natarajan S;Insaan A;Yoshioka H;Mori Y;Tsukahara S;Baskar S;Manjunath SR;Senthilkumar R;Thamaraikannan P;Srinivasan T;Preethy S;Abraham SJ
通讯作者：
Abraham SJ
影响因子：
2.1
作者：
Faydaci, Gokhan;Tarhan, Fatih;Ozgul, Aydin
通讯作者：
Ozgul, Aydin