ArticleTissue engineering and regenerative medicine2024
Improving Granulosa Cell Function in Premature Ovarian Failure with Umbilical Cord Mesenchymal Stromal Cell Exosome-Derived hsa_circ_0002021.
Article in Tissue engineering and regenerative medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Applications of Exosomes in Female Medicine: A Systematic Review of Molecular Biology, Diagnostic and Therapeutic Perspectives.International journal of molecular sciences · 2026Pooled it
- Circular RNAs as regulators and biomarkers of mammalian ovarian ageing.GeroScience · 2026Review
- ROS: their roles in diminished ovarian reserve.Frontiers in endocrinology · 2026Review
- Roles of exosomes in microenvironment-related premature ovarian insufficiency: mechanisms and therapeutic intervention.Reproductive biology and endocrinology : RB&E · 2025Review
- Current status and future prospects of mesenchymal stem cell-derived exosomes therapy for premature ovarian insufficiency.Journal of ovarian research · 2025Review
- Circular RNAs and mammalian follicular development: current insights and future prospects-an updated review.Cell death discovery · 2025Review
- The Role of Ovarian Granulosa Cells Related-ncRNAs in Ovarian Dysfunctions: Mechanism Research and Clinical Exploration.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- hUMSC-derived exosomes alleviate follicular interstitial cell autophagy by let-7a-5p/AMPK/mTOR axis in POI rats.Stem cell research & therapy · 2025Article
- Extracellular vesicles in stem cell-based gonadal regeneration: mechanisms, therapeutic potential, and translational challenges.Frontiers in veterinary science · 2025Review
- Therapeutic Efficacy and Promise of Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles in Aging and Age-Related Disorders.International journal of molecular sciences · 2024Review
- Hypoxic mesenchymal stem cell-derived exosomal circDennd2a regulates granulosa cell glycolysis by interacting with LDHA.Stem cell research & therapy · 2024Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
backgroundThe therapeutic potential of exosomes from human umbilical cord mesenchymal stem cells (HUMSCs-Exo) for delivering specific circular RNAs (circRNAs) in treating premature ovarian failure (POF) is not well understood. This study aimed to explore the efficacy of HUMSCs-Exo in delivering hsa_circ_0002021 for POF treatment, focusing on its effects on granulosa cell (GC) senescence and ovarian function.
methodsBioinformatic analysis was conducted on circRNA profiles using the GSE97193 dataset from GEO, targeting granulosa cells from varied age groups. To simulate granulosa cell senescence, KGN cells were treated with cyclophosphamide (CTX). HUMSCs were transfected with pcDNA 3.1 vectors to overexpress hsa_circ_0002021, and the HUMSCs-Exo secreted were isolated. These exosomes were characterized by transmission electron microscopy (TEM) and Western blotting to confirm exosomal markers CD9 and CD63. Co-culture of these exosomes with CTX-treated KGN cells was performed to assess β-galactosidase activity, oxidative stress markers, ROS levels, and apoptosis via flow cytometry. Interaction between hsa_circ_0002021, microRNA-125a-5p (miR-125a-5p), and cyclin-dependent kinase 6 (CDK6) was investigated using dual-luciferase assays and RNA immunoprecipitation (RIP). A POF mouse model was induced with CTX, treated with HUMSCs-Exo, and analyzed histologically and via immunofluorescence staining. Gene expression was quantified using RT-qPCR and Western blot.
resultshsa_circ_0002021 was under expressed in both in vivo and in vitro POF models and was effectively delivered by HUMSCs-Exo to KGN cells, showing a capability to reduce GC senescence. Overexpression of hsa_circ_0002021 in HUMSCs-Exo significantly enhanced these anti-senescence effects. This circRNA acts as a competitive adsorbent of miR-125a-5p, regulating CDK6 expression, which is crucial in modulating cell cycle and apoptosis. Enhanced expression of hsa_circ_0002021 in HUMSCs-Exo ameliorated GC senescence in vitro and improved ovarian function in POF models by modulating oxidative stress and cellular senescence markers.
conclusionThis study confirms that hsa_circ_0002021, when delivered through HUMSCs-Exo, can significantly mitigate GC senescence and restore ovarian function in POF models. These findings provide new insights into the molecular mechanisms of POF and highlight the therapeutic potential of circRNA-enriched exosomes in treating ovarian aging and dysfunction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.