动物学研究2023，Vol.44Issue(3) ：620-635.DOI:10.24272/j.issn.2095-8137.2022.340

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

Rui-Can Cao Yue Lv Gang Lu Hong-Bin Liu Wuming Wang Chunlai Tan Xian-Wei Su Zhiqiang Xiong Jin-Long Ma Wai-Yee Chan
动物学研究2023，Vol.44Issue(3) ：620-635.DOI:10.24272/j.issn.2095-8137.2022.340
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Extracellular vesicles from iPSC-MSCs alleviate chemotherapy-induced mouse ovarian damage via the ILK-PI3K/AKT pathway

Rui-Can Cao 1Yue Lv 2Gang Lu 3Hong-Bin Liu 4Wuming Wang 3Chunlai Tan 5Xian-Wei Su 6Zhiqiang Xiong 7Jin-Long Ma 4Wai-Yee Chan3
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作者信息

  • 1. 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
  • 2. 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
  • 3. 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
  • 4. 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
  • 5. 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
  • 6. 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
  • 7. SDIVF R&D Centre,12W,HKSTP,Hong Kong SAR,China
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Abstract

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.

Key words

Extracellular vesicles/Premature ovarian insufficiency/Human induced pluripotent stem cell-derived mesenchymal stem cells/ILK-PI3K/AKT pathway

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基金项目

CUHK VC Discretionary Fund provided to the Hong Kong Branch of Chinese Academy of Science Center for Excellence in Animal Ev(Acc 8601011)

National Key R&D Program(2021YFC2700500)

A-Smart Group to Shandong University and SDIVF R&D Centre Hong Kong()

Council General Research Fund (Hong Kong Special Administrative Region Government)(14103418)

出版年

2023
动物学研究
中国科学院昆明动物研究所 中国动物学会

动物学研究

CSTPCDCSCD
影响因子：0.582
ISSN：0254-5853
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