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Affecting 1% of women, POI causes infertility and systemic health complications. Current treatments focus on symptom management rather than restoring ovarian function. Mesenchymal stem cells (MSCs) offer promising regenerative potential through paracrine activity, immunomodulation, and tissue repair mechanisms. MSCs from various sources have demonstrated the ability to improve ovarian function, increase follicular survival, and restore hormone production in preclinical models. MSC-derived extracellular vesicles are emerging as cell-free alternatives with similar therapeutic effects. This review examines MSC mechanisms in ovarian restoration, evaluates current evidence, and discusses challenges in clinical translation for POI treatment.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical Abstract<\/jats:bold>\n          <\/jats:p>","DOI":"10.1007\/s12015-025-10944-2","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T02:04:00Z","timestamp":1754013840000},"page":"2089-2102","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Mesenchymal Stem Cells: A Therapeutic Approach in Fertility Restoration in Premature Ovarian Insufficiency"],"prefix":"10.1007","volume":"21","author":[{"given":"Nourhan","family":"Hassan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donia Mohamed","family":"Hussein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fady Ashraf","family":"Malak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazen Ashraf","family":"Abdelaziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Ibrahim","family":"Boushra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walid","family":"Shaalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emad M.","family":"Elzayat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"issue":"1","key":"10944_CR1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1093\/gerona\/glab252","volume":"77","author":"JB Mason","year":"2022","unstructured":"Mason, J. 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