Department of Urology, Nanjing First Hospital, Nanjing Medical University, No. 68 Changle Road, Nanjing, 210006, Jiangsu, China.
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Si Pai Lou 2, Nanjing, 210096, China.
Sci Rep. 2022 Mar 4;12(1):3573. doi: 10.1038/s41598-022-07472-1.
Urethral stricture (US) remains a challenging disease without effective treatment options due to the high recurrence rate. This study aims to evaluate the preventive effect of uncultured adipose derived stromal vascular fraction (SVF) on urethral fibrosis in a rat model of US. Results demonstrated that US rats displayed hyperechogenic urethral wall with a narrowed lumen compared with sham rats, while SVF rats exhibited less extensive urethral changes. By histology, US rats showed obvious submucosal fibrosis in the urethral specimens, while SVF rats exhibited mild submucosal fibrosis with less extensive tissue changes. Furthermore, US rats showed increased gene and protein expression of collagen I (2.0 ± 0.2, 2.2 ± 0.2, all were normalized against GAPDH, including the following), collagen III (2.5 ± 0.3, 1.2 ± 0.1), and TGFβ1R (2.8 ± 0.3, 1.9 ± 0.2), while SVF cells administration contributed to decreased gene and protein expression of collagen I (1.6 ± 0.2, 1.6 ± 0.2), collagen III (1.8 ± 0.4, 0.9 ± 0.1), and TGFβ1R (1.8 ± 0.3, 1.3 ± 0.2), in parallel with the improvement of vascularization and increased expression of VEGF (1.7 ± 0.1) and bFGF (3.1 ± 0.3). Additionally, SVF served anti-inflammatory effect through regulation of inflammatory cytokines and cells, accompanied with conversion of the macrophage phenotype. Our findings suggested that uncultured SVF presented an inhibitory effect on stricture formation at an early stage of urethral fibrosis.
尿道狭窄(US)仍然是一种具有挑战性的疾病,由于其高复发率,目前尚无有效的治疗方法。本研究旨在评估未培养脂肪来源的基质血管成分(SVF)对 US 大鼠模型尿道纤维化的预防作用。结果表明,与假手术大鼠相比,US 大鼠的尿道壁回声增强,管腔变窄,而 SVF 大鼠的尿道变化程度较轻。通过组织学观察,US 大鼠的尿道标本显示明显的黏膜下纤维化,而 SVF 大鼠表现为轻度的黏膜下纤维化,组织变化程度较轻。此外,US 大鼠的胶原 I(2.0±0.2、2.2±0.2,均相对于 GAPDH 归一化,包括以下)、胶原 III(2.5±0.3、1.2±0.1)和 TGFβ1R(2.8±0.3、1.9±0.2)的基因和蛋白表达增加,而 SVF 细胞给药有助于降低胶原 I(1.6±0.2、1.6±0.2)、胶原 III(1.8±0.4、0.9±0.1)和 TGFβ1R(1.8±0.3、1.3±0.2)的基因和蛋白表达,同时伴随着血管化的改善和 VEGF(1.7±0.1)和 bFGF(3.1±0.3)表达的增加。此外,SVF 通过调节炎症细胞因子和细胞发挥抗炎作用,同时伴随着巨噬细胞表型的转化。我们的研究结果表明,未培养的 SVF 在尿道纤维化的早期阶段对狭窄形成具有抑制作用。