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

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

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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.

Extracellular vesiclesPremature ovarian insufficiencyHuman induced pluripotent stem cell-derived mesenchymal stem cellsILK-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

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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

Shandong Key Laboratory of Reproductive Medicine,Shandong Provincial Hospital Affiliated to Shandong First Medical 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

SDIVF R&D Centre,12W,HKSTP,Hong Kong SAR,China

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CUHK VC Discretionary Fund provided to the Hong Kong Branch of Chinese Academy of Science Center for Excellence in Animal EvNational Key R&D ProgramA-Smart Group to Shandong University and SDIVF R&D Centre Hong KongCouncil General Research Fund (Hong Kong Special Administrative Region Government)

Acc 86010112021YFC270050014103418

2023

10.24272/j.issn.2095-8137.2022.340

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
年,卷(期)：2023.44(3)
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