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Extracellular vesicles from iPSC-MSCs alleviate chemotherapy-induced mouse ovarian damage via the ilk-pi3k/akt pathway

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Zoological Research 2023年第3期44卷 620-635页

作者： 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 Center for Reproductive Medicine Shandong UniversityJinanShandong 250012China Hong kong Branch of CAS Center for Excellence in Animal Evolution and Genetics The Chinese University of Hong KongHong Kong SARChina CUHk-SDU Joint Laboratory on Reproductive Genetics School of Biomedical SciencesFaculty of MedicineThe Chinese University of Hong KongHong Kong SARChina key Laboratory of Reproductive Endocrinology of Ministry of Education Shandong UniversityJinanShandong 250012China Shandong key Laboratory of Reproductive Medicine Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandong 250012China SDIVF R&D Centre 12WHKSTPHong Kong SARChina kunming Institute of Zoology-The Chinese University of Hong kong(kIZ-CUHk)Joint Laboratory of Bioresources and Molecular Research of Common Diseases Hong Kong SARChina

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 i PSC-MSC-EVs resulted in up-regulation of the integrinlinked 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.

关键词： Extracellular vesicles Premature ovarian insufficiency Human induced pluripotent stem cell-derived mesenchymal stem cells ilk-pi3k/akt pathway

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