研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

hUCMSC 来源的细胞外囊泡通过转移抗凋亡 miRNA 减轻顺铂诱导的小鼠颗粒细胞凋亡。

hUCMSC-derived extracellular vesicles relieve cisplatin-induced granulosa cell apoptosis in mice by transferring anti-apoptotic miRNAs.

发表日期:2024 Apr 25
作者: Wenjing Tang, Haiyan Yan, Xiaojun Chen, Yanan Pu, Xin Qi, Liyang Dong, Chuan Su
来源: GENES & DEVELOPMENT

摘要:

化疗引起的卵巢早衰(POI)是育龄女性癌症幸存者的常见并发症。间充质干细胞(MSC)移植和激素替代疗法等传统方法因其缺点而限制了临床应用,需要开发更多方法。在当前的研究中,在顺铂(CDDP)诱导的 POI 小鼠模型和人颗粒细胞(GC)系中研究了人脐带 MSC 衍生的细胞外囊泡(hUCMSC-EV)的潜在影响和潜在机制。结果表明,hUCMSC-EV 显着减轻中等剂量(1.5 mg/kg)CDDP 诱导的 POI 小鼠的体重减轻、卵巢重量减轻、卵巢萎缩和卵泡损失,与 hUCMSC 观察到的效果相似。我们进一步发现,hUCMSC-EVs可能通过上调GC中抗凋亡miRNA的水平,从而下调多个促凋亡基因的mRNA水平来抑制CDDP诱导的卵巢GC凋亡。总的来说,我们的研究结果表明,考虑到hUCMSC-EVs能有效挽救肿瘤治疗引起的卵巢损伤,中等剂量化疗可能是临床肿瘤治疗的更好选择。此外,hUCMSC-EV中的多种miRNA可能可用于抑制化疗引起的卵巢GC细胞凋亡,从而恢复卵巢功能并改善女性癌症患者的生活质量。
Premature ovarian insufficiency (POI) caused by chemotherapy is a common complication in female cancer survivors of childbearing age. Traditional methods including mesenchymal stem cell (MSC) transplant and hormone replacement therapy have limited clinical application due to their drawbacks, and more methods need to be developed. In the current study, the potential effects and underlying mechanisms of human umbilical cord MSC-derived extracellular vesicles (hUCMSC-EVs) were investigated in a cisplatin (CDDP)-induced POI mouse model and a human granulosa cell (GC) line. The results showed that hUCMSC-EVs significantly attenuated body weight loss, ovarian weight loss, ovary atrophy, and follicle loss in moderate-dose (1.5 mg/kg) CDDP-induced POI mice, similar to the effects observed with hUCMSCs. We further discovered that the hUCMSC-EVs might inhibit CDDP-induced ovarian GC apoptosis by upregulating anti-apoptotic miRNA levels in GCs, thereby downregulating the mRNA levels of multiple pro-apoptotic genes. In general, our findings indicate that moderate-dose chemotherapy may be a better choice for clinical oncotherapy considering the effective rescue of oncotherapy-induced ovarian damage with hUCMSC-EVs. Additionally, multiple miRNAs in hUCMSC-EVs may potentially be used to inhibit chemotherapy-induced ovarian GC apoptosis, thereby restoring ovarian function and improving the life quality of female cancer patients.