Evidence map›Paper›PMID 40270025›Full record

ArticleJournal of nanobiotechnology2025

M2 microglia-derived small extracellular vesicles modulate NSC fate after ischemic stroke via miR-25-3p/miR-93-5p-TGFBR/PTEN/FOXO3 axis.

Qian Zhang, Yan Yi, Tiange Chen, Ying Ai, Ziyang Chen, Ganzhi Liu, Zexuan Tang, Jianwei Chen, Tao Xu, Xin Chen and 2 more

Abstract read
In one paragraph

Article in Journal of nanobiotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Review
  2. Article
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  5. Review
  6. Article
  7. 3D-bioprinted adipose-derived stem cell-secreted GAS6Journal of nanobiotechnology · 2026
    Article
  8. The gut-brain axis: mechanisms linking intestinal dysbiosis with stroke.Frontiers in cell and developmental biology · 2026
    Review
  9. Review
  10. Review
  11. 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

12 authors.

Qian Zhang *Department of Neurosurgery, Xiangya Hospital Central South University, Changsha, Hunan, CN, 410008, China.
Yan Yi *Reproductive Medicine Center, Xiangya Hospital Central South University, Changsha, Hunan, CN, 410008, China.
Tiange ChenDepartment of Neurosurgery, Xiangya Hospital Central South University, Changsha, Hunan, CN, 410008, China.
Ying AiDepartment of Neurosurgery, Xiangya Hospital Central South University, Changsha, Hunan, CN, 410008, China.
Ziyang ChenDepartment of Neurosurgery, Xiangya Hospital Central South University, Changsha, Hunan, CN, 410008, China.
Ganzhi LiuDepartment of Neurosurgery, Xiangya Hospital Central South University, Changsha, Hunan, CN, 410008, China.
Zexuan TangSchool of Graduate Studies, Biomedical Science - Dental Scholars Track Program, Rutgers Biomedical and Health Sciences, Rutgers University, Newark, NJ, 07103, USA.
Jianwei ChenBio-Intelligent Manufacturing and Living Matter Bioprinting Center, Research Institute of Tsinghua University in Shenzhen, Tsinghua University, Shenzhen, China.
Tao XuBio-Intelligent Manufacturing and Living Matter Bioprinting Center, Research Institute of Tsinghua University in Shenzhen, Tsinghua University, Shenzhen, China.
Xin ChenDepartment of Neurosurgery, Xiangya Hospital Central South University, Changsha, Hunan, CN, 410008, China. chenxin1983@csu.edu.cn.
Jinfang LiuDepartment of Neurosurgery, Xiangya Hospital Central South University, Changsha, Hunan, CN, 410008, China. jinfang_liu@csu.edu.cn.
Yuguo XiaDepartment of Neurosurgery, Xiangya Hospital Central South University, Changsha, Hunan, CN, 410008, China. xiayuguo521@csu.edu.cn.

Funding

China Postdoctoral Science Foundation 2022M723562National Natural Science Foundation of China 82201543National Natural Science Foundation of China 82371407National Postdoctoral Program for Innovative Talents BX20220356Natural Science Foundation of Hunan Province 2024JJ5623Natural Science Foundation of Hunan Province 2024JJ6657Young Foundation of Xiangya hospital 2021Q01
6 · The paper itself

Abstract

backgroundEndogenous neurogenesis could promote stroke recovery. Furthermore, anti-inflammatory phenotypical microglia (M2-microglia) could facilitate Neural Stem Cell (NSC)-mediated neurogenesis following Ischemic Stroke (IS). Nonetheless, the mechanisms through which M2 microglia influence NSC-mediated neurogenesis post-IS remain unclear. On the other hand, M2 microglia-derived small Extracellular Vesicles (M2-sEVs) could exert phenomenal biological effects and play significant roles in cell-to-cell interactions, highlighting their potential involvement in NSC-mediated neurogenesis post-IS, forming the basis of this study.

methodsM2-sEVs were first isolated from IL-4-stimulated microglia. For in vivo tests, M2-sEVs were intravenously injected into mice every day for 14 days after transient Middle Cerebral Artery Occlusion (tMCAO). Following that, the infarct volume and neurological function, as well as NSC proliferation in the Subventricular Zone and dentate gyrus, migration, and differentiation in the infarct area, were examined. For in vitro tests, M2-sEVs were administered to NSC subjected to Oxygen-Glucose Deprivation (OGD) and then reoxygenation, after which NSC proliferation and differentiation were assessed. Finally, M2-sEVs were subjected to microRNA sequencing to explore the regulatory mechanisms.

resultsOur findings revealed that M2-sEVs reduced the infarct volume and increased the neurological score in mice post-tMCAO. Furthermore, M2-sEV treatment promoted NSC proliferation and neuronal differentiation both in vivo and in vitro. Additionally, microRNA sequencing revealed miR-93-5p and miR-25-3p enrichment in M2-sEVs. Inhibitors of these miRNAs prevented TGFBR, PTEN, and FOXO3 downregulation in NSC, reversing M2-sEVs' beneficial effects on neurogenesis and sensorimotor recovery.

conclusionsM2-sEVs increased NSC proliferation and neuronal differentiation, and protected against IS, at least partially, via delivering miR-25-3p and miR-93-5p to downregulate TGFBR, PTEN, and FOXO3 expression in NSC.

Indexed as

Extracellular VesiclesIschemic StrokeMicrogliaMicroRNAsNeural Stem CellsAnimalsCell DifferentiationCell ProliferationForkhead Box Protein O3Infarction, Middle Cerebral ArteryMaleMiceMice, Inbred C57BLNeurogenesisPTEN PhosphohydrolaseForkhead Box Protein O3FoxO3 protein, mouseMicroRNAsMIRN25 microRNA, mouseMirn93 microRNA, mousePTEN PhosphohydrolasePten protein, mouseIschemic stroke (IS)MicrogliaNeural stem cell (NSC)NeurogenesisSmall extracellular vesicles (sEVs)

Identifiers

PMID40270025
PMCPMC12020034

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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.