Evidence map›Paper›PMID 40955109›Full record

ArticleCNS neuroscience & therapeutics2025

Dual-Functionalized Extracellular Vesicles Promote Brain Repair and Remodeling Following Ischemic Stroke in Mice.

Victoria Shi, Shengju Wu, Qianyuan Lian, Rubing Shi, Ze Liu, Tongtong Xu, Shiyu Deng, Xinfa Shao, Anja Beckmann, Wanlu Li and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

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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

14 authors.

Victoria ShiShanghai Jiao Tong University Affiliated Sixth People's Hospital, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Shengju WuShanghai Jiao Tong University Affiliated Sixth People's Hospital, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Qianyuan LianShanghai Jiao Tong University Affiliated Sixth People's Hospital, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Rubing ShiShanghai Jiao Tong University Affiliated Sixth People's Hospital, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Ze LiuShanghai Jiao Tong University Affiliated Sixth People's Hospital, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Tongtong XuShanghai Jiao Tong University Affiliated Sixth People's Hospital, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Shiyu DengShanghai Jiao Tong University Affiliated Sixth People's Hospital, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Xinfa ShaoShanghai Jiao Tong University Affiliated Sixth People's Hospital, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Anja BeckmannDepartment of Anatomy and Cell Biology, Medical Faculty, Saarland University, Homburg/Saar, Germany.
Wanlu LiShanghai Jiao Tong University Affiliated Sixth People's Hospital, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Yaohui TangShanghai Jiao Tong University Affiliated Sixth People's Hospital, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Carola MeierDepartment of Anatomy and Cell Biology, Medical Faculty, Saarland University, Homburg/Saar, Germany.
Guo-Yuan YangShanghai Jiao Tong University Affiliated Sixth People's Hospital, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.ORCID 0000-0003-3105-9307
Zhijun ZhangShanghai Jiao Tong University Affiliated Sixth People's Hospital, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

Funding

National Key Research and Development Program of China 2019YFA0112000National Key Research and Development Program of China 2022YFA1603600National Natural Science Foundation of China 32301146National Natural Science Foundation of China 82271320National Natural Science Foundation of China 82371307National Natural Science Foundation of China 82571494Shanghai Rising-Star Program 21QA1405200
6 · The paper itself

Abstract

backgroundIschemic stroke remains a leading cause of long-term disability and mortality worldwide, with few effective treatment options. A key challenge in recovery is the brain's limited capacity to regenerate neurovascular structures after injury. To address this, we developed a dual-functionalized extracellular vesicle (EV) platform designed to enhance both targeting specificity and therapeutic efficacy for post-stroke repair.

methodsNeural stem cell-derived EVs were bioengineered via bio-click chemistry to display RGD peptides, enabling selective binding to integrin αVβ3, which is upregulated on activated endothelial cells in ischemic regions. EVs were concurrently loaded with vascular endothelial growth factor (VEGF), a pro-angiogenic and neurogenic cytokine that also enhances αVβ3 expression-thus creating a synergistic positive feedback mechanism to amplify targeting and tissue repair.

resultsEngineered EVs retained normal morphology and showed a 5.2-fold increase in endothelial uptake compared to naïve EVs (p < 0.01). In vitro, they significantly enhanced endothelial cell migration by 2.1-fold (p < 0.05). In a mouse model of transient middle cerebral artery occlusion (tMCAO), intravenously delivered dual-functionalized EVs preferentially accumulated in the ischemic hemisphere, reduced infarct volume by 52.4%, and improved motor coordination (rotarod latency) by 71.8% compared to PBS-treated controls (p < 0.05). Immunostaining revealed enhanced CD31+ microvessel density and increased Nestin+ neural stem and progenitor cell presence, indicating promotion of both angiogenesis and neurogenesis.

conclusionThis study presents a dual-functionalized EV system that combines targeted delivery with therapeutic reinforcement through VEGF loading, offering a potent and synergistic approach for ischemic stroke repair. These findings support further translational development of engineered EVs for neurovascular regeneration.

Indexed as

BrainExtracellular VesiclesIschemic StrokeAnimalsInfarction, Middle Cerebral ArteryMaleMiceMice, Inbred C57BLNeural Stem CellsVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Abioengineeringdrug deliveryextracellular vesiclesischemic strokeRGD peptidestem cell

Identifiers

PMID40955109
PMCPMC12437317

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.