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Extracellular vesicles from iPSC-MSCs alleviate chemotherapy-induced mouse ovarian damage via the ILK-PI3K/AKT pathway

摘要Chemotherapy can significantly reduce follicle counts in ovarian tissues and damage ovarian stroma, causing endocrine disorder, reproductive dysfunction, and primary ovarian insufficiency (POI). Recent studies have suggested that extracellular vesicles (EVs) secreted from mesenchymal stem cells (MSCs) exert therapeutic effects in various degenerative diseases. In this study,transplantation of EVs from human induced pluripotent stem cell-derived MSCs (iPSC-MSC-EVs) resulted in significant restoration of ovarian follicle numbers, improved granulosa cell proliferation, and inhibition of apoptosis in chemotherapy-damaged granulosa cells, cultured ovaries,and in vivo ovaries in mice. Mechanistically, treatment with iPSC-MSC-EVs resulted in up-regulation of the integrin-linked kinase (ILK) -PI3K/AKT pathway, which is suppressed during chemotherapy, most likely through the transfer of regulatory microRNAs (miRNAs) targeting ILK pathway genes. This work provides a framework for the development of advanced therapeutics to ameliorate ovarian damage and POI in female chemotherapy patients.

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作者 Rui-Can Cao [1] Yue Lv [2] Gang Lu [3] Hong-Bin Liu [4] Wuming Wang [3] Chunlai Tan [5] Xian-Wei Su [6] Zhiqiang Xiong [7] Jin-Long Ma [4] Wai-Yee Chan [3] 学术成果认领
作者单位 Center for Reproductive Medicine,Shandong University,Jinan,Shandong 250012,China;Hong Kong Branch of CAS Center for Excellence in Animal Evolution and Genetics,The Chinese University of Hong Kong,Hong Kong SAR,China;CUHK-SDU Joint Laboratory on Reproductive Genetics,School of Biomedical Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong SAR,China;Key Laboratory of Reproductive Endocrinology of Ministry of Education,Shandong University,Jinan,Shandong 250012,China;Kunming Institute of Zoology-The Chinese University of Hong Kong(KIZ-CUHK)Joint Laboratory of Bioresources and Molecular Research of Common Diseases,Hong Kong SAR,China [1] Hong Kong Branch of CAS Center for Excellence in Animal Evolution and Genetics,The Chinese University of Hong Kong,Hong Kong SAR,China;Shandong Key Laboratory of Reproductive Medicine,Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan,Shandong 250012,China [2] Hong Kong Branch of CAS Center for Excellence in Animal Evolution and Genetics,The Chinese University of Hong Kong,Hong Kong SAR,China;CUHK-SDU Joint Laboratory on Reproductive Genetics,School of Biomedical Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong SAR,China;Kunming Institute of Zoology-The Chinese University of Hong Kong(KIZ-CUHK)Joint Laboratory of Bioresources and Molecular Research of Common Diseases,Hong Kong SAR,China [3] Center for Reproductive Medicine,Shandong University,Jinan,Shandong 250012,China;CUHK-SDU Joint Laboratory on Reproductive Genetics,School of Biomedical Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong SAR,China;Key Laboratory of Reproductive Endocrinology of Ministry of Education,Shandong University,Jinan,Shandong 250012,China [4] Hong Kong Branch of CAS Center for Excellence in Animal Evolution and Genetics,The Chinese University of Hong Kong,Hong Kong SAR,China;CUHK-SDU Joint Laboratory on Reproductive Genetics,School of Biomedical Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong SAR,China [5] CUHK-SDU Joint Laboratory on Reproductive Genetics,School of Biomedical Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong SAR,China;Kunming Institute of Zoology-The Chinese University of Hong Kong(KIZ-CUHK)Joint Laboratory of Bioresources and Molecular Research of Common Diseases,Hong Kong SAR,China [6] SDIVF R&D Centre,12W,HKSTP,Hong Kong SAR,China [7]
DOI 10.24272/j.issn.2095-8137.2022.340
发布时间 2024-02-28
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动物学研究

动物学研究

2023年44卷3期

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