Department of Urology, No. 731 Hospital of China Aerospace Science and Industry Corporation, Beijing, China.
J Cell Mol Med. 2018 Nov;22(11):5607-5616. doi: 10.1111/jcmm.13834. Epub 2018 Sep 4.
The treatment of complicated long segment strictures remains to a challenge, and the substitution urethroplasty treatment is often accompanied by subsequent tissue fibrosis and secondary stricture formation. In situ injection of human adipose tissue-derived stem cells (hADSC) could potential be applied for prevention of urethral fibrosis, but the cells transplantation alone may be insufficient because of the complicated histopathological micro-environmental changes in the injury site. This study investigated whether miR-21 modification can improve the therapeutic efficacy of ADSCs against urethral fibrosis to limit urethral stricture recurrence. MiR-21-modified ADSCs (miR-21) were constructed via lentivirus-mediated transfer of pre-miR-21 and GFP reporter gene. In vitro results suggested that miR-21 modification can increase the angiogenesis genes expression of ADSCs and enhance its anti-oxidative effects against reactive oxygen species (ROS) damage. In vivo results showed that miR-21 modification contributes to increased urodynamic parameters and better formation of the epithelium and the muscle layer as compared to ADSCs transplantation alone groups. The results demonstrated that miR-21 modification in ADSCs could improve urethral wound healing microenvironment, enhance stem cell survival through ROS scavenging and promote the neovascularization via regulating angiogenic genes expression, which eventually increase the ADSCs' therapeutic potential for urethral wound healing.
复杂的长段狭窄的治疗仍然是一个挑战，替代尿道成形术治疗常伴有随后的组织纤维化和继发性狭窄形成。人脂肪组织源性干细胞（hADSC）的原位注射可能潜在地应用于预防尿道纤维化，但由于损伤部位复杂的组织病理学微环境变化，单独细胞移植可能是不够的。本研究探讨了 miR-21 修饰是否可以提高 ADSC 治疗尿道纤维化的疗效，以限制尿道狭窄的复发。通过慢病毒介导的前 miR-21 和 GFP 报告基因转导构建了 miR-21 修饰的 ADSC（miR-21）。体外结果表明，miR-21 修饰可以增加 ADSC 的血管生成基因表达，并增强其对活性氧（ROS）损伤的抗氧化作用。体内结果表明，与单独 ADSC 移植组相比，miR-21 修饰有助于增加尿动力学参数，并更好地形成上皮和肌肉层。结果表明，miR-21 修饰可改善尿道创伤愈合微环境，通过清除 ROS 增强干细胞的存活，并通过调节血管生成基因表达促进新血管生成，从而最终增加 ADSC 治疗尿道创伤愈合的潜力。
