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源自羊水干细胞的外泌体miR-10a在化疗后可保护卵巢卵泡。

Exosomal miR-10a derived from amniotic fluid stem cells preserves ovarian follicles after chemotherapy.

作者信息

Xiao Guan-Yu, Cheng Chun-Chun, Chiang Yih-Shien, Cheng Winston Teng-Kuei, Liu I-Hsuan, Wu Shinn-Chih

机构信息

Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.

The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.

出版信息

Sci Rep. 2016 Mar 16;6:23120. doi: 10.1038/srep23120.


DOI:10.1038/srep23120
PMID:26979400
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4793229/
Abstract

Chemotherapy (CTx)-induced premature ovarian failure (POF) in woman remains clinically irreversible. Amniotic fluid stem cells (AFSCs) have shown the potential to treat CTx-induced POF; however, the underlying mechanism is unclear. Here we demonstrate that AFSC-derived exosomes recapitulate the anti-apoptotic effect of AFSCs on CTx-damaged granulosa cells (GCs), which are vital for the growth of ovarian follicles. AFSC-derived exosomes prevent ovarian follicular atresia in CTx-treated mice via the delivery of microRNAs in which both miR-146a and miR-10a are highly enriched and their potential target genes are critical to apoptosis. The down-regulation of these two miRNAs in AFSC-derived exosomes attenuates the anti-apoptotic effect on CTx-damaged GCs in vitro. Further, the administration of these miRNAs recapitulates the effects both in vitro and in vivo, in which miR-10a contributes a dominant influence. Our findings illustrate that miR-10a has potential as a novel therapeutic agent for the treatment of POF.

摘要

化疗(CTx)诱导的女性卵巢早衰(POF)在临床上仍然不可逆转。羊水干细胞(AFSCs)已显示出治疗CTx诱导的POF的潜力;然而,其潜在机制尚不清楚。在此我们证明,AFSC衍生的外泌体重现了AFSCs对CTx损伤的颗粒细胞(GCs)的抗凋亡作用,而颗粒细胞对卵泡生长至关重要。AFSC衍生的外泌体通过递送微小RNA来预防CTx处理小鼠的卵巢卵泡闭锁,其中miR-146a和miR-10a高度富集,且它们的潜在靶基因对细胞凋亡至关重要。AFSC衍生外泌体中这两种微小RNA的下调减弱了对体外CTx损伤的GCs的抗凋亡作用。此外,这些微小RNA的给药在体外和体内均重现了其作用,其中miR-10a起主要作用。我们的研究结果表明,miR-10a有潜力作为治疗POF的新型治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d62/4793229/830e4e0eed37/srep23120-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d62/4793229/5d77873d01e3/srep23120-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d62/4793229/dbcf16514771/srep23120-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d62/4793229/48b15590f20d/srep23120-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d62/4793229/830e4e0eed37/srep23120-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d62/4793229/5d77873d01e3/srep23120-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d62/4793229/dbcf16514771/srep23120-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d62/4793229/48b15590f20d/srep23120-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d62/4793229/830e4e0eed37/srep23120-f4.jpg

相似文献

[1]
Exosomal miR-10a derived from amniotic fluid stem cells preserves ovarian follicles after chemotherapy.

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[2]
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引用本文的文献

[1]
Potential MiRNA therapies for premature ovarian failure: new challenges and opportunities.

Stem Cell Res Ther. 2025-7-15

[2]
The revolutionary role of placental derivatives in biomedical research.

Bioact Mater. 2025-3-19

[3]
Non-coding RNA-mediated granulosa cell dysfunction during ovarian aging: From mechanisms to potential interventions.

Noncoding RNA Res. 2025-3-3

[4]
The Role of Exosomal miRNAs in Female Infertility: Therapeutic Potential and Mechanisms of Action.

Stem Cell Rev Rep. 2025-3-24

[5]
Human urine stem cells protect against cyclophosphamide-induced premature ovarian failure by inhibiting SLC1A4-mediated outflux of intracellular serine in ovarian granulosa cells.

Cell Mol Biol Lett. 2025-2-19

[6]
Mesenchymal stem cell-derived extracellular vesicles therapy for primary ovarian insufficiency: a systematic review and meta-analysis of pre-clinical studies.

J Ovarian Res. 2024-10-14

[7]
Clusterin-carrying extracellular vesicles derived from human umbilical cord mesenchymal stem cells restore the ovarian function of premature ovarian failure mice through activating the PI3K/AKT pathway.

Stem Cell Res Ther. 2024-9-13

[8]
Stem cell-derived extracellular vesicles in premature ovarian failure: an up-to-date meta-analysis of animal studies.

J Ovarian Res. 2024-9-9

[9]
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Noncoding RNA Res. 2024-7-20

[10]
Insight on "the Effect of Human Umbilical Cord Mesenchymal Stem Cell on Premature Ovarian Cell Senilism Through miR-10a" [Letter].

Int J Womens Health. 2024-8-16

本文引用的文献

[1]
Noncoding RNAs regulate NF-κB signaling to modulate blood vessel inflammation.

Front Genet. 2014-12-10

[2]
Amniotic fluid stem cells prevent follicle atresia and rescue fertility of mice with premature ovarian failure induced by chemotherapy.

PLoS One. 2014-9-8

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Overexpression of miR-146a in basal-like breast cancer cells confers enhanced tumorigenic potential in association with altered p53 status.

Carcinogenesis. 2014-8-14

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J Control Release. 2014-8-2

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miR-146a ameliorates liver ischemia/reperfusion injury by suppressing IRAK1 and TRAF6.

PLoS One. 2014-7-2

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Exosomes as critical agents of cardiac regeneration triggered by cell therapy.

Stem Cell Reports. 2014-5-8

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A p53-dependent tumor suppressor network is induced by selective miR-125a-5p inhibition in multiple myeloma cells.

J Cell Physiol. 2014-12

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Human amniotic epithelial cells can differentiate into granulosa cells and restore folliculogenesis in a mouse model of chemotherapy-induced premature ovarian failure.

Stem Cell Res Ther. 2013-10-14

[9]
miR-181b promotes cell proliferation and reduces apoptosis by repressing the expression of adenylyl cyclase 9 (AC9) in cervical cancer cells.

FEBS Lett. 2013-11-20

[10]
Human amniotic fluid stem cells have a potential to recover ovarian function in mice with chemotherapy-induced sterility.

BMC Dev Biol. 2013-9-4

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