ArticleJournal of ovarian research2025
PEDF-Expressing mesenchymal stem cells restore ovarian function via Tim-3-Mediated immune modulation in primary ovarian failure.
Article in Journal of ovarian research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Beyond Potency: Emerging Determinants and Optimization Strategies Enhancing Therapeutic Efficacy of Adult Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Progress in research on the effects of Platelet-Rich Plasma (PRP) ovarian injection on early ovarian reserve dysfunction and premature ovarian insufficiency.Journal of ovarian research · 2026Review
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Authors and funding
4 authors.
Funding
Abstract
backgroundPrimary ovarian failure (POF), characterized by premature ovarian dysfunction, remains a therapeutic challenge due to limited interventions addressing its immune dysregulation. Regulatory T cells (Tregs) and immune checkPOFnt pathways, such as Tim-3, are critical yet underexplored targets. Pigment epithelium-derived factor (PEDF), an immunomodulatory protein, offers promise for enhancing mesenchymal stem cell (MSC) therapy in POF.
methodsUsing a cyclophosphamide-induced POF mouse model, we evaluated the therapeutic potential of PEDF-overexpressing bone marrow MSCs (BMSCs-PEDF). Mice were stratified into PBS, adenovirus-delivered PEDF (AD-PEDF), control BMSCs (BMSCs-LacZ), and BMSCs-PEDF groups. Outcomes included ovarian index, follicular histology, Treg cell populations, Tim-3/Gal-9 expression, and serum hormone/cytokine profiles.
resultsBMSCs-PEDF outperformed other treatments, significantly restoring estrous cyclicity (2.1-fold increase in vaginal exfoliated cells vs. AD-PEDF, P < 0.05) and ovarian index (1.8-fold higher vs. AD-PEDF, P < 0.01). Histology revealed a 3.5-fold increase in viable follicles, with reduced atresia. Mechanistically, BMSCs-PEDF expanded Tim-3 + CD4 + CD25 + Tregs (4.2-fold vs. PBS) and upregulated ovarian Tim-3/Gal-9 expression (3.7-fold vs. AD-PEDF, P < 0.001), correlating with suppressed IFN-γ (62% reduction) and restored estrogen (2.4-fold increase) and progesterone levels.
conclusionThis study demonstrates that PEDF-engineered BMSCs rejuvenate ovarian function by dual mechanisms: enhancing Treg-mediated immune tolerance via the Tim-3/Gal-9 axis and promoting follicular survival. These findings position BMSCs-PEDF as a transformative, mechanism-driven therapy for POF, with broad implications for autoimmune-related infertility.
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