Evidence map›Paper›PMID 41582652›Full record

ArticleStem cells translational medicine2026

Extracellular vesicles derived from differentiated granulosa-like cells restore the ovarian function of rats with premature ovarian insufficiency.

Cheng Zou, Zelan Yang, Yan Zou, Hanyu Xiao, Yufei Deng, Jin Bai, Liaoqiong Fang, Zhibiao Wang

Abstract read
In one paragraph

Article in Stem cells translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Cheng ZouState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China.ORCID 0009-0008-9694-8862
Zelan YangState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China.
Yan ZouState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China.
Hanyu XiaoState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China.
Yufei DengState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China.
Jin BaiState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China.
Liaoqiong FangState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China.
Zhibiao WangState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China.

Funding

Chongqing Talents Project of the Chongqing Municipal Science and Technology Bureau cstc2021ycjh-bgzxm0021
6 · The paper itself

Abstract

Specifically differentiated cells exhibit greater therapeutic efficacy than mesenchymal stem cells (MSCs), and extracellular vesicles (EVs) present therapeutic benefits similar to those of parental cells and fewer safety issues. Ovarian granulosa cells (OGCs) play a critical role in the pathogenesis of premature ovarian insufficiency (POI), a common gynecological disease that can cause infertility and has no effective treatment. Here, we investigated whether umbilical cord mesenchymal stem cells (UCMSCs) can differentiate into ovarian granulosa-like cells (GLCs) and whether GLC-EVs are more effective in restoring ovarian function than UCMSC-EVs are in POI model rats. Here, we differentiated rat UCMSCs (rUCMSCs) into GLCs in vitro using cytokines and hormones and isolated GLC-EVs. We then used chemotherapy-induced POI model rats to verify the ability of GLC-EVs to repair ovarian function. We found that GLCs/GLCs-EVs expressed granulosa cell markers (FOXL2 and FSHR). We demonstrated that GLC-EVs outperformed rUCMSC-EVs by restoring the estrous cycle and ovarian morphology, increasing the number of follicles, regulating serum hormone levels, and restoring fertility in POI model rats. Mechanistically, GLC-EVs showed enhanced ovarian tropism. Proteomic analysis identified PLAU as a key component of GLC-EVs, and subsequent antibody blockade experiments demonstrated that PLAU contributes to primordial follicle activation through promoting FOXO3A phosphorylation (pFOXO3A). This study provides the first proof that EVs derived from differentiated cells enhance therapeutic precision for POI, improve the tissue targeting of EV therapy, and provide a generalized strategy for clinical cell-free therapy.

Indexed as

Extracellular VesiclesGranulosa CellsMesenchymal Stem CellsOvaryPrimary Ovarian InsufficiencyAnimalsCell DifferentiationDisease Models, AnimalFemaleRatsRats, Sprague-Dawleydifferentiationgranulosa-like cellovarian granulosa cell (OGC)premature ovarian insufficiency (POI)umbilical cord mesenchymal stem cell (UCMSC)

Identifiers

PMID41582652
PMCPMC12832956

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.