Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
Stem Cells Transl Med. 2019 Apr;8(4):383-391. doi: 10.1002/sctm.18-0063. Epub 2018 Dec 19.
Torsion-detorsion (T/D)-induced testicular injury may lead to male subfertility and even infertility. Stem cell therapy provides an alternative to attenuate testicular injury and promote spermatogenesis. Adipose-derived stromal vascular fraction (SVF) can be acquired conveniently without in vitro expansion, which may avoid the potential risks of microbial contamination, xenogenic nutritional sources, etc., during cell culture. In this study, we investigate the protective effects of autologous uncultured SVF on testicular injury and spermatogenesis in a rat model of T/D. Animals were randomly divided into sham, T/D+ phosphate-buffered saline, and T/D + SVF groups (18 rats in each group). SVF was isolated, labeled with lipophilic fluorochrome chloromethylbenzamido dialkylcarbocyanine, and transplanted into T/D testis by local injection. At 3, 7, 14, and 28 days F surgery, testicular tissue and serum samples were harvested for histopathological, immunohistochemical, Western blot, and enzyme-linked immunosorbent assays. Histopathological findings demonstrated severe injury in the testis with decreased Johnsen's score led by T/D, while uncultured SVF reduced testicular injury and elevated the decreased score. Injected SVF cells were mainly integrated into interstitial region and seminiferous tubules, enhanced the secretion of basic fibroblast growth factor and stem cell factor in the testis, contributed to the declining level of malondialdehyde and restoration of hormonal homeostasis, and then reduced the injury of Leydig cells and germ cells, as well as promoting spermatogenesis. Our findings demonstrated that autologous uncultured SVF could protect the testis from testicular ischemia-reperfusion injury and promote spermatogenesis, which provide significant clinical implications for the prevention of infertility induced by testicular T/D. Stem Cells Translational Medicine 2019;8:383-391.
扭转-扭转(T/D)诱导的睾丸损伤可导致男性不育甚至不孕。干细胞疗法为减轻睾丸损伤和促进生精提供了一种替代方法。脂肪来源的基质血管部分(SVF)可以方便地获得,无需体外扩增,这可以避免细胞培养过程中微生物污染、异种营养源等潜在风险。在这项研究中,我们研究了自体未培养的 SVF 对 T/D 大鼠模型睾丸损伤和生精的保护作用。动物随机分为假手术组、T/D+磷酸盐缓冲液组和 T/D+SVF 组(每组 18 只大鼠)。SVF 分离后,用亲脂性荧光染料氯甲基苯甲酰胺二烷基碳氰化标记,并通过局部注射移植到 T/D 睾丸。在 F 手术后 3、7、14 和 28 天,采集睾丸组织和血清样本进行组织病理学、免疫组织化学、Western blot 和酶联免疫吸附测定。组织病理学检查结果表明,T/D 导致睾丸严重损伤,Johnsen 评分降低,而未培养的 SVF 可减轻睾丸损伤,提高降低的评分。注射的 SVF 细胞主要整合到间质区和生精小管中,增强了睾丸中碱性成纤维细胞生长因子和干细胞因子的分泌,有助于降低丙二醛水平和恢复激素平衡,从而减少了睾丸间质细胞和生精细胞的损伤,并促进了生精。我们的研究结果表明,自体未培养的 SVF 可保护睾丸免受睾丸缺血再灌注损伤并促进生精,这为预防睾丸 T/D 引起的不育提供了重要的临床意义。《干细胞转化医学》2019 年;8:383-391。