Evidence map›Paper›PMID 40538064›Full record

ArticleClinical and translational medicine2025

Engineered small extracellular vesicles for targeted delivery of perlecan to stabilise the blood-spinal cord barrier after spinal cord injury.

Wei Peng, Wentao Zhang, Wei Cui, Wenjin Chen, Yin Zhuang, Rupeng Chu, Jinghua Tan, Jingbo Xue, Yiguo Yan, Guoyong Yin and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical and translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Targeted HAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Review
  4. Review
  5. Review
  6. Advanced small extracellular vesicles delivery systems forExtracellular vesicles and circulating nucleic acids · 2026
    Review
  7. 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.

Wei PengDepartment of Spine Surgery, Wuxi Ninth People's Hospital Affiliated to Soochow University, Wuxi, China.
Wentao ZhangDepartment of Cardiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.ORCID 0009-0005-3905-4342
Wei CuiDepartment of Spine Surgery, Wuxi Ninth People's Hospital Affiliated to Soochow University, Wuxi, China.
Wenjin ChenDepartment of Spine Surgery, Wuxi Ninth People's Hospital Affiliated to Soochow University, Wuxi, China.
Yin ZhuangDepartment of Spine Surgery, Wuxi Ninth People's Hospital Affiliated to Soochow University, Wuxi, China.
Rupeng ChuDepartment of Spine Surgery, Wuxi Ninth People's Hospital Affiliated to Soochow University, Wuxi, China.
Jinghua TanDepartment of Spine Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
Jingbo XueDepartment of Spine Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
Yiguo YanDepartment of Spine Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
Guoyong YinDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Shujun ZhangDepartment of Spine Surgery, Wuxi Ninth People's Hospital Affiliated to Soochow University, Wuxi, China.
Yong XieDepartment of Spine Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.

Funding

Entrepreneurship and Innovation Doctoral Program of Jiangsu Province 2023SCBS01General Project of Wuxi Municipal Health Commission M202002Natural Science Foundation of Hunan Province 2025JJ60555Research Foundation of Education Bureau of Hunan Province 24B0395Science and Technology Bureau of Wuxi K20221063Wuxi 9th Affiliated Hospital of Soochow University QD202301Wuxi 9th Affiliated Hospital of Soochow University YB202105
6 · The paper itself

Abstract

backgroundDestruction of the blood-spinal cord barrier (BSCB) following spinal cord injury (SCI) can result in various harmful cytokines, neutrophils, and macrophages infiltrating into the injured site, causing secondary damage. Growing evidence shows that M2 macrophages and their small extracellular vesicles (sEVs) contribute to tissue repair in various diseases. METHODS AND

resultsIn our previous proteomics-based analysis of protein expression profiles in M2 macrophages and their sEVs (M2-sEVs), the proteoglycan perlecan, encoded by HSPG2, was found to be upregulated in M2-sEVs. Perlecan is a crucial component of basement membranes, playing a vital role in stabilising BSCB homeostasis and functions through its interactions with other matrix components, growth factors, and receptors. Here, we verified the high levels and remarkable therapeutic effect of M2-sEV-derived perlecan on the permeability of spinal cord microvascular endothelial cells exposed to oxygen glucose deprivation and reoxygenation in vitro. We also decorated the surface of M2-sEVs with a fusion protein comprising the N-terminus of Lamp2 and arginine glycine aspartic acid (RGD) peptides, which have an affinity for integrin αvβ3 and are primarily present on neovascular endothelium surfaces. In SCI model mice, these RGD-M2-sEVs accumulated at injured sites, promoting BSCB restoration. Finally, we identified M2-sEV-derived perlecan as a key player in regulating BSCB integrity and functional recovery post-SCI.

conclusionOur results indicate that RGD-M2-sEVs promote BSCB restoration by transporting perlecan to neovascular endothelial cells, representing a potential strategy for SCI treatment. KEY POINTS: Perlecan, a crucial component of basement membranes that plays a vital role in stabilising BSCB homeostasis and functions, was found to be upregulated in M2-sEVs. M2-sEVs decorated with RGD peptide can effectively target the neovascular endothelium surfaces at the injured spinal cord site. RGD-M2-sEVs promote BSCB restoration by transporting perlecan to neovascular endothelial cells, representing a potential strategy for SCI treatment.

Indexed as

Extracellular VesiclesHeparan Sulfate ProteoglycansSpinal Cord InjuriesAnimalsFemaleMiceSpinal CordHeparan Sulfate ProteoglycansperlecanBlood‒spinal cord barrier repairM2 macrophagePerlecanRGD peptideSmall extracellular vesiclesSpinal cord injury

Identifiers

PMID40538064
PMCPMC12179339

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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.