Evidence map›Paper›PMID 40560785›Full record

ArticleJournal of extracellular vesicles2025

Cortical Actin Depolymerisation in 3D Cell Culture Enhances Extracellular Vesicle Secretion and Therapeutic Effects.

Zhen Yang, Xiaoke Li, Qiyuan Lin, Fanfan Zhou, Kaini Liang, Jiao Jiao Li, Yudi Niu, Qingchen Meng, Tianyuan Zhao, Hao Li and 8 more

Erratum issuedAbstract read
In one paragraph

Article in Journal of extracellular vesicles, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. A 3D Astrocyte Microenvironment Model Enables Rapid CaAdvanced healthcare materials · 2026
    Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Zhen YangArthritis Clinical and Research Center, Peking University People's Hospital, Beijing, China.
Xiaoke LiDepartment of Orthopaedics, Shanxi Medical University Second Affiliated Hospital, Taiyuan, China.
Qiyuan LinArthritis Clinical and Research Center, Peking University People's Hospital, Beijing, China.
Fanfan ZhouArthritis Clinical and Research Center, Peking University People's Hospital, Beijing, China.
Kaini LiangSchool of Biomedical Engineering, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.
Jiao Jiao LiSchool of Biomedical Engineering, Faculty of Engineering and IT, University of Technology Sydney, Sydney, Australia.
Yudi NiuSchool of Biomedical Engineering, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.
Qingchen MengArthritis Clinical and Research Center, Peking University People's Hospital, Beijing, China.
Tianyuan ZhaoDepartment of Orthopedics, Peking University Third Hospital, Beijing, China.
Hao LiInstitute of Orthopedics, the First Medical Center, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, China.
Du WangArthritis Clinical and Research Center, Peking University People's Hospital, Beijing, China.
Jianjing LinDepartment of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen, China.
Hui LiArthritis Clinical and Research Center, Peking University People's Hospital, Beijing, China.
Bin WangDepartment of Orthopaedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Wei LiuBeijing CytoNiche Biotechnology Co. Ltd, Beijing, China.
Yanan DuSchool of Biomedical Engineering, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.
Jianhao LinArthritis Clinical and Research Center, Peking University People's Hospital, Beijing, China.
Dan XingArthritis Clinical and Research Center, Peking University People's Hospital, Beijing, China.ORCID https://orcid.org/0000-0001-6966-3134

Funding

National Key Research and Development Program of China 2024YFA1108603National Natural Science Foundation of China 82272538National Natural Science Foundation of China 82472482Natural Science Foundation of Beijing Municipality L222087Outstanding Doctoral Students of Peking University Health Science CenterPeking University Clinical Scientist Training Program, supported by the Fundamental Research Funds for the Central Universities BMU2024PYJH015
6 · The paper itself

Abstract

Three-dimensional (3D) culture systems have been shown to enhance cellular secretion of small extracellular vesicles (sEVs) compared to two-dimensional (2D) culture. However, the molecular mechanisms driving sEV secretion and influencing their potential for disease treatment have not been elucidated. In this study, we discovered the depolymerisation of cortical actin as a new mechanism that leads to increased sEV release, and that in 3D cultured mesenchymal stem cells (MSCs), this process was modulated by the downregulation of integrin-α1 (ITGA1) and subsequent inhibition of the RhoA/cofilin signalling pathway. Interestingly, the knockdown of Rab27A and Rab27B significantly reduced sEV secretion by MSCs to 0.5- and 0.1-fold, respectively. However, there was no difference in expression levels of Rab27A/B between MSCs cultured in 2D and 3D environments. In addition, sEVs derived from 3D cultured MSCs demonstrated enhanced therapeutic function both in vitro and in rat models of osteoarthritis (OA) and wound healing. Collectively, this study illustrates a new mechanism for enhanced secretion of sEVs, involving RhoA/cofilin pathway-dependent cortical actin depolymerisation, which is independent of Rab27A/B. These findings provide novel insights for optimising the yield of stem cell-derived sEVs, as well as their therapeutic efficacy for treating chronic diseases.

Indexed as

ActinsExtracellular VesiclesMesenchymal Stem CellsAnimalsCell Culture Techniques, Three DimensionalCells, CulturedHumansMalerab27 GTP-Binding Proteinsrab GTP-Binding ProteinsRatsRats, Sprague-DawleyrhoA GTP-Binding ProteinSignal TransductionWound HealingActinsrab27 GTP-Binding Proteinsrab GTP-Binding ProteinsrhoA GTP-Binding Protein3D cultureactin depolymerisationcortical actinRab27A/Bsmall extracellular vesicles

Identifiers

PMID40560785
PMCPMC12190546

What OpenQuestion holds

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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 OpenQuestion graph.