Extracellular vesicles from iPSC-MSCs alleviate chemotherapy-induced mouse ovarian damage via the ILK-PI3K/AKT pathway
作者机构:Center for Reproductive MedicineShandong UniversityJinanShandong 250012China Hong Kong Branch of CAS Center for Excellence in Animal Evolution and GeneticsThe Chinese University of Hong KongHong Kong SARChina CUHK-SDU Joint Laboratory on Reproductive GeneticsSchool of Biomedical SciencesFaculty of MedicineThe Chinese University of Hong KongHong Kong SARChina Key Laboratory of Reproductive Endocrinology of Ministry of EducationShandong UniversityJinanShandong 250012China Shandong Key Laboratory of Reproductive MedicineShandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandong 250012China SDIVF R&D Centre12WHKSTPHong Kong SARChina Kunming Institute of Zoology-The Chinese University of Hong Kong(KIZ-CUHK)Joint Laboratory of Bioresources and Molecular Research of Common DiseasesHong Kong SARChina
出 版 物:《Zoological Research》 (动物学研究(英文))
年 卷 期:2023年第44卷第3期
页 面:620-635页
核心收录:
学科分类:1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金: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)
主 题:Extracellular vesicles Premature ovarian insufficiency Human induced pluripotent stem cell-derived mesenchymal stem cells ILK-PI3K/AKT pathway
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 *** 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 ***,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 *** work provides a framework for the development of advanced therapeutics to ameliorate ovarian damage and POI in female chemotherapy patients.