ArticleStem cell research & therapy2024
Clusterin-carrying extracellular vesicles derived from human umbilical cord mesenchymal stem cells restore the ovarian function of premature ovarian failure mice through activating the PI3K/AKT pathway.
Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The improvement of umbilical cord mesenchymal stem cells on the ovarian microenvironment: a systematic review and meta-analysis.Journal of ovarian research · 2026Pooled it
- Maternal hyperhomocysteinemia compromises female offspring fertility through overactivation of primordial follicles.iScience · 2026Article
- Extracellular vesicles as therapeutic agents for retinal ganglion cell degeneration: current challenges and future prospects.International ophthalmology · 2026Review
- Immediate protective effect of rUCMSC-EVs on ovarian function in a cyclophosphamide -induced premature ovarian insufficiency rats: counteracting granulosa cell apoptosis.Journal of ovarian research · 2026Article
- Mesenchymal stem cell therapy for premature ovarian insufficiency: progress and challenges.Journal of ovarian research · 2026Review
- Extracellular vesicles derived from differentiated granulosa-like cells restore the ovarian function of rats with premature ovarian insufficiency.Stem cells translational medicine · 2026Article
- A Two-Hit Hypothesis for Chemotherapy-Induced Primary Ovarian Insufficiency in Asian Populations: A Population-Specific Mechanistic Framework Linking Genetic Susceptibility and Cytotoxic Stress via the PI3K-AKT-FOXO3 Axis.BioMed research international · 2026Review
- Preventing ovarian aging: from redox-targeted strategies to extracellular vesicle-based therapies.Frontiers in aging · 2026Review
- Quantification of EV-associated miRNA in liquid biopsies for biomarker signature development.Extracellular vesicles and circulating nucleic acids · 2026Review
- [Stem cell therapy for premature ovarian insufficiency: a review of clinical evidence and therapeutic strategies].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025Review
- Mesenchymal stem cells and their promise in reversing ovarian aging.Journal of ovarian research · 2025Review
- Oxidoreductase delivery by cell therapies in cyclophosphamide-induced premature ovarian insufficiency: a mechanistic insight into ovarian rejuvenation.Journal of ovarian research · 2025Article
- Mesenchymal stem cells derived extracellular vesicles ameliorate ovarian aging through inhibiting LGALS3BP/NF-κB induced inflammation.Journal of ovarian research · 2025Article
- Article
- Research on the mechanism of human umbilical cord mesenchymal stem cells and their extracellular vesicles in the treatment of common reproductive diseases.Stem cell research & therapy · 2025Review
- Study on the Function ofAnimals : an open access journal from MDPI · 2025Article
- The cutting-edge progress of novel biomedicines in ovulatory dysfunction therapy.Acta pharmaceutica Sinica. B · 2025Review
- Extracellular vesicle-based drug overview: research landscape, quality control and nonclinical evaluation strategies.Signal transduction and targeted therapy · 2025Review
- Extracellular vesicle-enriched secretome of adipose-derived stem cells upregulates clusterin to alleviate doxorubicin-induced apoptosis in cardiomyocytes.Biology direct · 2025Article
- Precision medicine in premature ovarian insufficiency: a focus on the precision therapeutic strategies for mesenchymal stem cells.Stem cell research & therapy · 2025Review
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Authors and funding
13 authors.
Funding
Abstract
backgroundEmerging evidence has highlighted the therapeutic potential of human umbilical cord mesenchymal stem cells (UC-MSCs) in chemotherapy-induced premature ovarian failure (POF). This study was designed to investigate the appropriate timing and molecular mechanism of UC-MSCs treatment for chemotherapy-induced POF.
methodsOvarian structure and function of mice were assessed every 3 days after injections with cyclophosphamide (CTX) and busulfan (BUS). UC-MSCs and UC-MSCs-derived extracellular vesicles (EVs) were infused into mice via the tail vein, respectively. Ovarian function was analyzed by follicle counts, the serum levels of hormones and ovarian morphology. The apoptosis and proliferation of ovarian granulosa cells were analyzed in vitro and in vivo. Label-free quantitative proteomics was used to detect the differentially expressed proteins in UC-MSC-derived EVs.
resultsAfter CTX/BUS injection, we observed that the ovarian function of POF mice was significantly deteriorated on day 9 after CTX/BUS infusion. TUNEL assay indicated that the number of apoptotic cells in the ovaries of POF mice was significantly higher than that in normal mice on day 3 after CTX/BUS injection. Transplantation of UC-MSCs on day 6 after CTX/BUS injection significantly improved ovarian function, enhanced proliferation and inhibited apoptosis of ovarian granulosa cells, whereas the therapeutic effect of UC-MSCs transplantation decreased on day 9, or day 12 after CTX/BUS injection. Moreover, EVs derived from UC-MSCs exerted similar therapeutic effects on POF. UC-MSCs-derived EVs could activate the PI3K/AKT signaling pathway and reduce ovarian granulosa cell apoptosis. Quantitative proteomics analysis revealed that clusterin (CLU) was highly expressed in the EVs of UC-MSCs. The supplementation of CLU proteins prevented ovarian granulosa cells from chemotherapy-induced apoptosis. Further mechanistic analysis showed that CLU-knockdown blocked the PI3K/AKT signaling and reversed the protective effects of UC-MSCs-derived EVs.
conclusionsAdministration of UC-MSCs and UC-MSCs-derived EVs on day 6 of CTX/BUS injection could effectively improve the ovarian function of POF mice. UC-MSCs-derived EVs carrying CLU promoted proliferation and inhibited apoptosis of ovarian granulosa cells through activating the PI3K/AKT pathway. This study identifies a previously unrecognized molecular mechanism of UC-MSCs-mediated protective effects on POF, which pave the way for the use of cell-free therapeutic approach for POF.
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