Li Muxin, Yang Tianli, Zhao Jun, Ma Xinghua, Cao Yuanyuan, Hu Xiaojie, Zhao Shuli, Zhou Liuhua
General Clinical Research Center, Nanjing First Hospital, China Pharmaceutical University, Nanjing, Jiangsu, China.
Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Mater Today Bio. 2024 Feb 29;25:101012. doi: 10.1016/j.mtbio.2024.101012. eCollection 2024 Apr.
Urethral stricture (US) is a common disease in urology, lacking effective treatment options. Although injecting a stem cells suspension into the affected area has shown therapeutic benefits, challenges such as low retention rate and limited efficacy hinder the clinical application of stem cells. This study evaluates the therapeutic impact and the mechanism of adipose-derived vascular fraction (SVF) combined with cell sheet engineering technique on urethral fibrosis in a rat model of US. The results showed that SVF-cell sheets exhibit positive expression of α-SMA, CD31, CD34, Stro-1, and eNOS. In vivo study showed less collagen deposition, low urethral fibrosis, and minimal tissue alteration in the group receiving cell sheet transplantation. Furthermore, the formation of a three-dimensional (3D) tissue-like structure by the cell sheets enhances the paracrine effect of SVF, facilitates the infiltration of M2 macrophages, and suppresses the TGF-β/Smad2 pathway through HGF secretion, thereby exerting antifibrotic effects. Small animal in vivo imaging demonstrates improved retention of SVF cells at the damaged urethra site with cell sheet application. Our results suggest that SVF combined with cell sheet technology more efficiently inhibits the early stages of urethral fibrosis.
尿道狭窄（US）是泌尿外科的一种常见疾病，缺乏有效的治疗方法。尽管将干细胞悬液注射到患病区域已显示出治疗效果，但诸如保留率低和疗效有限等挑战阻碍了干细胞的临床应用。本研究评估了脂肪源性血管成分（SVF）联合细胞片工程技术对US大鼠模型尿道纤维化的治疗作用及其机制。结果显示，SVF细胞片呈现α-SMA、CD31、CD34、Stro-1和eNOS的阳性表达。体内研究表明，接受细胞片移植的组中胶原沉积减少、尿道纤维化程度低且组织改变最小。此外，细胞片形成的三维（3D）组织样结构增强了SVF的旁分泌作用，促进M2巨噬细胞浸润，并通过分泌肝细胞生长因子（HGF）抑制TGF-β/Smad2通路，从而发挥抗纤维化作用。小动物体内成像显示，应用细胞片后SVF细胞在受损尿道部位的保留有所改善。我们的结果表明，SVF联合细胞片技术能更有效地抑制尿道纤维化的早期阶段。
