Effect of uncultured adipose-derived stromal vascular fraction on preventing urethral stricture formation in rats

Liuhua Zhou,Zheng Xu,Feng Zhao,Ran Wu,Luwei Xu,Hua Xu,Tianli Yang,Zhongle Xu,Kaiwei Song,Changcheng Zhou,Zhiqiang Qin,Ruipeng Jia

doi:10.1038/s41598-022-07472-1

Abstract

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.

Highlights

Urethral stricture (US) remains a challenging disease without effective treatment options due to the high recurrence rate
We aimed to explore the potential effect of uncultured stromal vascular fraction (SVF) cells in alleviating urethral spongiofibrosis and promoting urethral tissue repair in a rat model of US
Flow cytometric analysis demonstrated that uncultured SVF cells expressed hematopoietic (CD11b/c [39.35 ± 7.62%], CD34 [15.50 ± 5.23%], CD45 [40.50 ± 7.22%], and CD133 [15.43 ± 4.57]), mesenchymal (CD90 [38.60 ± 6.11%] and CD106 [32.12 ± 9.21%]), and endothelial (CD31 [13.32 ± 5.50%] and VEGFR2 [20.37 ± 5.89%]) markers, indicating a heterogeneous population of SVF cells (Fig. 1)