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

被引:13
作者
Cao, Rui-Can [1 ,2 ,3 ,4 ,7 ]
Lv, Yue [2 ,5 ]
Lu, Gang [2 ,3 ,7 ]
Liu, Hong-Bin [1 ,3 ,4 ]
Wang, Wuming [2 ,3 ,7 ]
Tan, Chunlai [2 ,3 ]
Su, Xian-Wei [3 ,7 ]
Xiong, Zhiqiang [6 ]
Ma, Jin-Long [1 ,3 ,4 ]
Chan, Wai-Yee [2 ,3 ,7 ]
机构
[1] Shandong Univ, Ctr Reprod Med, Jinan 250012, Shandong, Peoples R China
[2] Chinese Univ Hong Kong, CAS Ctr Excellence Anim Evolut & Genet, Hong Kong Branch, Hong Kong, Peoples R China
[3] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, CUHK SDU Joint Lab Reprod Genet, Hong Kong, Peoples R China
[4] Shandong Univ, Key Lab Reprod Endocrinol, Minist Educ, Jinan 250012, Shandong, Peoples R China
[5] Shandong First Med Univ, Shandong Prov Hosp, Shandong Key Lab Reprod Med, Jinan, Peoples R China
[6] HKSTP, SDIVF R&D Ctr, 12W, Hong Kong, Peoples R China
[7] Kunming Inst Zool Chinese Univ Hong Kong KIZ CUHK, Hong Kong, Peoples R China
关键词
Extracellular vesicles; Premature ovarian insufficiency; Human induced pluripotent stem cell-derived mesenchymal stem cells; ILK-PI3K; AKT pathway; INTEGRIN-LINKED KINASE; INTEGRATION; CELLS; ILK; CYCLOPHOSPHAMIDE; LOCALIZATION; ACTIVATION; PROPOSAL; REPAIR;
D O I
10.24272/j.issn.2095-8137.2022.340
中图分类号
Q95 [动物学];
学科分类号
071002 ;
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.
引用
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页码:620 / +
页数:19
相关论文
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  • [61] [张伟宏 Zhang Weihong], 2014, [中国应用生理学杂志, Chinese Journal of Applied Physiology], V30, P85