Evidence map›Paper›PMID 40361250›Full record

ArticleStem cell research & therapy2025

Mesenchymal stem cells derived from hPSC via neural crest attenuate chemotherapy-induced premature ovarian insufficiency by ameliorating apoptosis and oxidative stress in granulosa cells.

Xinran Li, Jinrong Liao, Youhong Zheng, Wei Cai, Jie Chen, Yu Liang, Yuanmei Chen, Xiaoxuan Li, Jiamao Luo, Jiaxin Xie and 7 more

Abstract read
In one paragraph

Article in Stem cell research & therapy, 2025. 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

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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

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

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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

17 authors.

Xinran Li *Obstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Jinrong Liao *Obstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Youhong Zheng *Obstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Wei CaiObstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Jie ChenObstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Yu LiangObstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Yuanmei ChenObstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Xiaoxuan LiObstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Jiamao LuoObstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Jiaxin XieObstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Manping ZhouObstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Lilin HangObstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Xiujuan SunObstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Xin YueObstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Xuefeng WangDepartment of Obstetrics and Gynecology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, China. 15913130306@163.com.
Yifeng WangObstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China. wyf1988@163.com.
Huiyan WangObstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China. huiyanwang1990@163.com.

Funding

National Natural Science Foundation of China 82001501
6 · The paper itself

Abstract

backgroundPremature ovarian insufficiency (POI) poses a significant threat to female reproductive health and currently lacks effective interventions. Recent studies highlight the promising potential of human pluripotent stem cell-derived mesenchymal stem cells (hPSC-MSC) in regenerative medicine. However, research on hPSC-MSC-based treatments for POI remains limited, particularly in the characterization of the intermediate differentiation stages from hPSC to MSC. This study presents an accelerated differentiation protocol for generating hPSC-MSC via neural crest cells (NCC) and evaluates their therapeutic potential in chemotherapy-induced POI.

methodsWe modified a canonical small molecule-mediated protocol for hPSC-NCC-MSC differentiation. Systematic characterization of differentiated-cells was performed using qPCR, immunofluorescence, cell viability assays, flow cytometry and trilineage differentiation. In vivo, hPSC-NCC-MSC were transplanted into chemotherapy-induced POI SD rat models, and parameters such as body weight, ovarian weight, estrous cycle, hormone levels, follicle count, and mating were assessed. Granulosa cells (GC) apoptosis was analyzed using TUNEL assay and immunohistochemistry. In vitro, their effects on apoptosis inhibition and oxidative stress alleviation were investigated in a cultured GC cell line. Additionally, comparisons between umbilical cord MSC (UC-MSC) and hPSC-NCC-MSC in chemotherapy-induced POI was conducted.

resultsOur optimized protocol, combining CHIR99021 and SB431542, efficiently induced NCC from both human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC). The programmed hPSC-NCC-MSC, characterized by specific NCC markers (P75, HNK1, SOX10, and AP2α), exhibited typical MSC morphology, trilineage differentiation potential, favorable cell viability, and prominent anti-senescence properties. Among these, NCC differentiated from H1-hESCs (H1-NCC) demonstrated the highest induction efficiency (72.45%), and H1-NCC-derived MSC (H1-NCC-MSC) displayed superior proliferation and anti-senescence properties compared to UC-MSC. Besides, H1-NCC-MSC exhibited therapeutic efficacy comparable to UC-MSC in both in vivo and in vitro models of chemotherapy-induced POI, potentially through mechanisms involving reduced GC apoptosis, alleviated oxidative stress, and improved mitochondrial function.

conclusionsOur findings propose a modified hPSC-NCC-MSC differentiation protocol, offering an inexhaustible and stable source for regenerative therapies. Furthermore, we provide the first experimental evidence that hPSC-NCC-MSC have therapeutic potential comparable to UC-MSC in restoring chemotherapy-induced POI. The underlying mechanisms are likely associated with paracrine-mediated effects on GC apoptosis, oxidative stress, and mitochondrial dysfunction.

Indexed as

ApoptosisGranulosa CellsMesenchymal Stem CellsMesenchymal Stem Cell TransplantationNeural CrestOxidative StressPluripotent Stem CellsPrimary Ovarian InsufficiencyAnimalsAntineoplastic AgentsCell DifferentiationFemaleHumansRatsRats, Sprague-DawleyAntineoplastic AgentsCyclophosphamideGranulosa cellsHuman pluripotent stem cellsMesenchymal stem cellsNeural crest cellsOxidative stressPremature ovarian insufficiency

Identifiers

PMID40361250
PMCPMC12076839

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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.