Department of Reproductive Biology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Hum Exp Toxicol. 2024 Jan-Dec;43:9603271241269019. doi: 10.1177/09603271241269019.
Several studies investigated the application of Mesenchymal stem cells (MSCs) for treating spermatogenic disorders. Considering the limitation of MSC application, the present study aimed to compare Wharton's jelly MSCs secretomes, including condition medium (CM) 10-fold concentrated (CM10), 20-fold concentrated CM (CM20), and extracellular vesicles (EVs) to restore busulfan-induced damage on male mice reproduction. So, Wharton's jelly MSCs were cultured, CM was collected, and EVs were isolated. Seventy-two mice were randomly assigned to nine groups, including Control, Busulfan 1 month (1M), Busulfan 2 months (2M), CM10, Busulfan + CM10, CM20, Busulfan + CM20, EVs, and Busulfan + EVs groups. Sperm characteristics, DNA maturity, DNA fragmentation index (DFI), and testicular gene expression were evaluated. Data analysis revealed that CM10 significantly improved sperm plasma membrane integrity, sperm DNA maturity, and DFI in the Busulfan + CM10 group compared to the Busulfan 2M group. Although CM20 and EVs showed a non-significant improvement. Gene expression analysis showed busulfan administration significantly decreased the expression of AR, CREB1, and PLCζ genes, while CM10 significantly restored CREB1 gene expression. The present study demonstrated that CM10 is more effective than CM20 or EVs in reducing busulfan-induced reproductive toxicity.
多项研究探讨了间充质干细胞（MSCs）在治疗精子发生障碍中的应用。鉴于 MSC 应用的局限性，本研究旨在比较 Wharton 胶 MSC 分泌组，包括 10 倍浓缩条件培养基（CM10）、20 倍浓缩 CM（CM20）和细胞外囊泡（EVs），以恢复白消安诱导的雄性小鼠生殖损伤。因此，培养 Wharton 胶 MSC，收集 CM 并分离 EVs。72 只小鼠被随机分为 9 组，包括对照组、白消安 1 个月（1M）组、白消安 2 个月（2M）组、CM10 组、白消安+CM10 组、CM20 组、白消安+CM20 组、EVs 组和白消安+EVs 组。评估精子特征、DNA 成熟度、DNA 碎片化指数（DFI）和睾丸基因表达。数据分析显示，与白消安 2M 组相比，CM10 组可显著改善白消安+CM10 组精子质膜完整性、精子 DNA 成熟度和 DFI。尽管 CM20 和 EVs 显示出非显著改善。基因表达分析显示，白消安处理显著降低了 AR、CREB1 和 PLCζ 基因的表达，而 CM10 则显著恢复了 CREB1 基因的表达。本研究表明，CM10 比 CM20 或 EVs 更能有效降低白消安诱导的生殖毒性。
