Luo Peng, Chen Xuren, Gao Feng, Xiang Andy Peng, Deng Chunhua, Xia Kai, Gao Yong
Department of Urology and Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China.
Biomedicines. 2024 Jan 3;12(1):98. doi: 10.3390/biomedicines12010098.
Testicular aging is associated with diminished fertility and certain age-related ailments, and effective therapeutic interventions remain elusive. Here, we probed the therapeutic efficacy of exosomes derived from human umbilical cord mesenchymal stem cells (hUMSC-Exos) in counteracting testicular aging.
We employed a model of 22-month-old mice and administered intratesticular injections of hUMSC-Exos. Comprehensive analyses encompassing immunohistological, transcriptomic, and physiological assessments were conducted to evaluate the effects on testicular aging. Concurrently, we monitored alterations in macrophage polarization and the oxidative stress landscape within the testes. Finally, we performed bioinformatic analysis for miRNAs in hUMSC-Exos.
Our data reveal that hUMSC-Exos administration leads to a marked reduction in aging-associated markers and cellular apoptosis while promoting cellular proliferation in aged testis. Importantly, hUMSC-Exos facilitated the restoration of spermatogenesis and elevated testosterone synthesis in aged mice. Furthermore, hUMSC-Exos could attenuate inflammation by driving the phenotypic shift of macrophages from M1 to M2 and suppress oxidative stress by reduced ROS production. Mechanistically, these efficacies against testicular aging may be mediated by hUMSC-Exos miRNAs.
Our findings suggest that hUMSC-Exos therapy presents a viable strategy to ameliorate testicular aging, underscoring its potential therapeutic significance in managing testicular aging.
睾丸衰老与生育能力下降及某些与年龄相关的疾病有关，有效的治疗干预措施仍然难以捉摸。在此，我们探讨了人脐带间充质干细胞来源的外泌体（hUMSC-Exos）在对抗睾丸衰老方面的治疗效果。
我们采用22月龄小鼠模型，进行睾丸内注射hUMSC-Exos。进行了包括免疫组织学、转录组学和生理学评估在内的综合分析，以评估对睾丸衰老的影响。同时，我们监测了睾丸内巨噬细胞极化和氧化应激状态的变化。最后，我们对hUMSC-Exos中的miRNA进行了生物信息学分析。
我们的数据显示，给予hUMSC-Exos可显著降低衰老相关标志物和细胞凋亡，同时促进老年睾丸中的细胞增殖。重要的是，hUMSC-Exos促进了老年小鼠精子发生的恢复和睾酮合成的增加。此外，hUMSC-Exos可通过促使巨噬细胞从M1型向M2型转变来减轻炎症，并通过减少活性氧的产生来抑制氧化应激。从机制上讲，这些对抗睾丸衰老的功效可能由hUMSC-Exos的miRNA介导。
我们的研究结果表明，hUMSC-Exos疗法是改善睾丸衰老的一种可行策略，突显了其在管理睾丸衰老方面的潜在治疗意义。
