2. Academic Validation
  3. Mesenchymal stem cell-derived small extracellular vesicles loaded with miRNA-4488 alleviate chemotherapy-induced premature ovarian insufficiency via mitigation of apoptosis and oxidative stress

Mesenchymal stem cell-derived small extracellular vesicles loaded with miRNA-4488 alleviate chemotherapy-induced premature ovarian insufficiency via mitigation of apoptosis and oxidative stress

  • Biomater Adv. 2026 Apr:181:214656. doi: 10.1016/j.bioadv.2025.214656.
Shi-Xian Li 1,  Shi-Yao Wei 1,  Chai Li 1,  Ya-Le Sheng 1,  Yun Liu 2,  Na Xu 3
Affiliations

Affiliations

  • 1 College of Life Sciences and Health, Institute of Advanced Materials and Nanotechnology, Wuhan University of Science and Technology, Wuhan, 430065, PR China.
  • 2 Department of Obstetrics and Gynecology, Xiangyang Central Hospital, Hubei University of Arts and Sciences, Xiangyang, 441021, PR China. Electronic address: [email protected].
  • 3 College of Life Sciences and Health, Institute of Advanced Materials and Nanotechnology, Wuhan University of Science and Technology, Wuhan, 430065, PR China. Electronic address: [email protected].
PMID: 41406654 DOI: 10.1016/j.bioadv.2025.214656
Abstract

Chemotherapy-induced premature ovarian insufficiency (POI) can disrupt endocrine homeostasis in female Cancer patients. Since current therapeutic options remain inadequate, there is an urgent need to develop new strategies for POI prevention or treatment. Small extracellular vesicles (sEVs) derived from stem cells are recognized for their capacities in tissue repair, regeneration, and drug delivery. In this study, a MicroRNA delivery system was constructed by loading miRNA-4488 into bone marrow mesenchymal stem cell-derived sEVs via electroporation. The prepared sEVs-miR4488 significantly inhibited macrophage inflammation and promoted fibroblast cell migration and proliferation. In oxaliplatin-induced ovarian granulosa cells, sEVs-miR4488 reduced the expression of Bax and increased the expression of Bcl-2, demonstrating the anti-apoptotic activity. Additionally, oxaliplatin-induced Reactive Oxygen Species production and mitochondrial depolarization were both decreased following treatment with sEVs-miR4488. These therapeutic effects were further confirmed in a POI mouse model. Bioinformatics analysis using FunRich and GO-BP revealed the involvement of multiple signaling pathways, and the NF-κB signaling pathway was verified to be downregulated in the protective mechanism mediated by miR-4488. Collectively, it provides a new strategy for the prevention and treatment of POI using sEVs-miR4488 in this study.

Keywords

Exosome; Extracellular vesicles; Mesenchymal stem cells; Premature ovarian insufficiency; miR-4488.

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