Guo Hailin, Sa Yinglong, Huang Jianwen, Wang Zhou, Wang Lin, Xie Minkai, Lv Xiangguo
Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Urol Int. 2016;96(2):223-30. doi: 10.1159/000440667. Epub 2015 Oct 17.
To evaluate the effect of tissue inhibitor of metalloproteinase-1 small interfering RNA (TIMP-1 siRNA) transfected fibroblasts (FB) for urethral reconstruction.
A ventral urethral mucosal defect was created. Substitution urethroplasty was performed with small intestinal submucosa (SIS) alone (8 rabbits, group 1), autogenic oral keratinocytes (OK)-seeded SIS (8 rabbits, group 2) or autogenic OK and TIMP-1 siRNA transfected FB-seeded SIS (8 rabbits, group 3). At 1 and 6 months after surgery (4 rabbits at each time point), retrograde urethrogram and histologic analysis were performed to evaluate the outcomes of urethroplasty.
TIMP-1 siRNA transfected FB decreased the secretion of type I collagen. Under retrograde urethrography, 5 rabbits in group 1, 6 in group 2 and 7 in group 3 maintained a wide urethral caliber. Histologically, inflammation and fibrosis were observed at 6 months in group 1. The speed of urothelium, smooth muscle and vessel regeneration in group 3 was faster than that in group 2. Comparison of smooth muscle-to-collagen ratio, epithelial layers, smooth muscle content and microvessel density among three groups revealed a significant increase (p < 0.05).
TIMP-1 siRNA transfected FB could be used as a source of seed cell for urethral tissue engineering and could prevent the proliferation of urethral scar tissue.
评估金属蛋白酶组织抑制剂-1小干扰RNA（TIMP-1 siRNA）转染的成纤维细胞（FB）用于尿道重建的效果。
制作腹侧尿道黏膜缺损。分别采用单纯小肠黏膜下层（SIS）（8只兔，第1组）、接种自体口腔角质形成细胞（OK）的SIS（8只兔，第2组）或接种自体OK和TIMP-1 siRNA转染FB的SIS（8只兔，第3组）进行替代尿道成形术。术后1个月和6个月（每个时间点4只兔），进行逆行尿道造影和组织学分析以评估尿道成形术的效果。
TIMP-1 siRNA转染的FB减少了I型胶原的分泌。逆行尿道造影显示，第1组5只兔、第2组6只兔和第3组7只兔尿道口径较宽。组织学检查发现，第1组在6个月时出现炎症和纤维化。第3组尿路上皮、平滑肌和血管再生速度比第2组快。三组之间平滑肌与胶原比例、上皮层数、平滑肌含量和微血管密度的比较显示有显著增加（p < 0.05）。
TIMP-1 siRNA转染的FB可作为尿道组织工程的种子细胞来源，并可防止尿道瘢痕组织增生。
