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

doi:10.24272/j.issn.2095-8137.2022.340

Volume 44 Issue 3

May 2023

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Article Navigation > Zoological Research > 2023 > 44(3): 620-635

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. Extracellular vesicles from iPSC-MSCs alleviate chemotherapy-induced mouse ovarian damage via the ILK-PI3K/AKT pathway. Zoological Research, 2023, 44(3): 620-635. doi: 10.24272/j.issn.2095-8137.2022.340

Citation:

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. Extracellular vesicles from iPSC-MSCs alleviate chemotherapy-induced mouse ovarian damage via the ILK-PI3K/AKT pathway. Zoological Research, 2023, 44(3): 620-635. doi: 10.24272/j.issn.2095-8137.2022.340

Citation:

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. Extracellular vesicles from iPSC-MSCs alleviate chemotherapy-induced mouse ovarian damage via the ILK-PI3K/AKT pathway. Zoological Research, 2023, 44(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

doi: 10.24272/j.issn.2095-8137.2022.340

Rui-Can Cao^{1, 2, 3, 4, 7},
Yue Lv^{2, 5},
Gang Lu^{2, 3, 7},
Hong-Bin Liu^{1, 3, 4},
Wuming Wang^{2, 3, 7},
Chunlai Tan^{2, 3},
Xian-Wei Su^{3, 7},
Zhiqiang Xiong⁶,
Jin-Long Ma^{1, 3, 4
,
,},
Wai-Yee Chan^{2, 3, 7
,
,}

1.
Center for Reproductive Medicine, Shandong 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
3.
CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
4.
Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China
5.
Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250012, China
6.
SDIVF R&D Centre, 12W, HKSTP, Hong Kong SAR, China
7.
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

The raw RNA-seq data were deposited in the NCBI Sequence Read Archive (SRA) (BioProjectID PRJNA916119), GSA Database (Accession No. CRA009327), and Science Data Bank (DOI:10.57760/sciencedb.j00139.00048). The raw miRNA-seq data were deposited in the NCBI SRA (BioProjectID PRJNA915756), GSA Database (Accession No. HRA003686), and Science Data Bank (DOI 10.57760/sciencedb.j00139.00047).
Supplementary data to this article can be found online.
The authors declare that they have no competing interests.
W.Y.C., J.L.M., G.L., and R.C.C. contributed to project conception. J.L.M., G.L., H.B.L., and W.Y.C. contributed to funding acquisition. R.-C.C. conducted experiments. Y.L., R.C.C, X.W.S., and Z.Q.X. analyzed data and prepared the figures and manuscript. W.M.W., C.L.T., and Y.L. provided technical support. All authors read and approved the final version of the manuscript.

Funds: This work was supported by the CUHK VC Discretionary Fund provided to the Hong Kong Branch of Chinese Academy of Science Center for Excellence in Animal Evolution and Genetics (Acc 8601011), the National Key R&D Program (2021YFC2700500), A-Smart Group to Shandong University and SDIVF R&D Centre Hong Kong, and Research Grants Council General Research Fund (Hong Kong Special Administrative Region Government) (14103418)

More Information

Corresponding author: E-mail: majinlong_sdu@163.com; chanwy@cuhk.edu.hk
Received Date: 2022-10-26
Accepted Date: 2023-03-01

Published Online: 2023-03-02

Publish Date: 2023-05-18

Abstract

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.

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References(60)

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