Liu Yang, Ma Wenjun, Liu Bo, Wang Yangcai, Chu Jiaqiang, Xiong Geng, Shen Lianju, Long Chunlan, Lin Tao, He Dawei, Butnaru Denis, Alexey Lyundup, Zhang Yuanyuan, Zhang Deying, Wei Guanghui
Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Child Urogenital Development and Tissue Engineering, Chongqing, 400014, China.
Stem Cell Res Ther. 2017 Mar 9;8(1):63. doi: 10.1186/s13287-017-0500-y.
Urethral reconstruction is one of the great surgical challenges for urologists. A cell-based tissue-engineered urethra may be an alternative for patients who have complicated long strictures and need urethral reconstruction. Here, we demonstrated the feasibility of using autologous urine-derived stem cells (USCs) seeded on small intestinal submucosa (SIS) to repair a urethral defect in a rabbit model.
Autologous USCs were obtained and characterized, and their capacity to differentiate into urothelial cells (UCs) and smooth muscle cells (SMCs) was tested. Then, USCs were labeled with PKH67, seeded on SIS, and transplanted to repair a urethral defect. The urethral defect model was surgically established in New Zealand white male rabbits. A ventral urethral gap was created, and the urethral mucosa was completely removed, with a mean rabbit penile urethra length of 2 cm. The urethral mucosal defect was repaired with a SIS scaffold (control group: SIS with no USCs; experimental group: autologous USC-seeded SIS; n = 12 for each group). A series of tests, including a retrograde urethrogram, histological analysis, and immunofluorescence, was undertaken 2, 3, 4, and 12 weeks after the operation to evaluate the effect of the autologous USCs on urethral reconstruction.
Autologous USCs could be easily collected and induced to differentiate into UCs and SMCs. In addition, the urethral caliber, speed of urothelial regeneration, content of smooth muscle, and vessel density were significantly improved in the group with autologous USC-seeded SIS. Moreover, inflammatory cell infiltration and fibrosis were found in the control group with only SIS, but not in the experimental autologous USC-seeded SIS group. Furthermore, immunofluorescence staining demonstrated that the transplanted USCs differentiated into UCs and SMCs in vivo.
Autologous USCs can be used as an alternative cell source for cell-based tissue engineering for urethral reconstruction.
尿道重建是泌尿外科医生面临的重大手术挑战之一。对于患有复杂长段狭窄且需要尿道重建的患者，基于细胞的组织工程化尿道可能是一种替代方案。在此，我们证明了在兔模型中使用接种于小肠黏膜下层（SIS）的自体尿液来源干细胞（USCs）修复尿道缺损的可行性。
获取并鉴定自体USCs，测试其分化为尿路上皮细胞（UCs）和平滑肌细胞（SMCs）的能力。然后，用PKH67标记USCs，接种于SIS上，并移植以修复尿道缺损。在新西兰雄性白兔中通过手术建立尿道缺损模型。制造腹侧尿道间隙，完全去除尿道黏膜，兔阴茎尿道平均长度为2厘米。用SIS支架修复尿道黏膜缺损（对照组：无USCs的SIS；实验组：接种自体USCs的SIS；每组n = 12）。术后2、3、4和12周进行一系列测试，包括逆行尿道造影、组织学分析和免疫荧光，以评估自体USCs对尿道重建的效果。
自体USCs易于收集，并可诱导分化为UCs和SMCs。此外，接种自体USCs的SIS组的尿道管径、尿路上皮再生速度、平滑肌含量和血管密度均有显著改善。而且，仅含SIS的对照组发现有炎性细胞浸润和纤维化，而接种自体USCs的SIS实验组未发现。此外，免疫荧光染色显示移植的USCs在体内分化为UCs和SMCs。
自体USCs可作为基于细胞的组织工程用于尿道重建的替代细胞来源。
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