Evidence map›Paper›PMID 38500170›Full record

ArticleJournal of biomedical science2024

Engineered extracellular vesicles carrying let-7a-5p for alleviating inflammation in acute lung injury.

Sin-Yu Chen, Yi-Ling Chen, Po-Chen Li, Tai-Shan Cheng, Yeh-Shiu Chu, Yi-Shan Shen, Hsin-Tung Chen, Wei-Ni Tsai, Chien-Ling Huang, Martin Sieber and 10 more

Open access · diamondAbstract read
In one paragraph

Article in Journal of biomedical science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
6.1field-weighted citation impact, top 3% of its field
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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

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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

20 authors at 9 institutions in 2 countries.

Sin-Yu Chen *Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan.ORCID http://orcid.org/0009-0003-9399-4330
Yi-Ling Chen *Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan.
Po-Chen LiInstitute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan.
Tai-Shan ChengInstitute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan.
Yeh-Shiu ChuBrain Research Center, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan.
Yi-Shan ShenDepartment of Orthopedic Surgery, Far Eastern Memorial Hospital, New Taipei City, 220216, Taiwan.
Hsin-Tung ChenInstitute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan.
Wei-Ni TsaiInstitute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan.
Chien-Ling HuangInstitute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan.
Martin SieberBionet Therapeutics, Taipei, 114065, Taiwan.
Yuan-Chieh YehDepartment of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, 204201, Taiwan.
Hsiao-Sheng LiuDepartment of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, 701401, Taiwan.
Chi-Ling ChiangDepartment of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, 43210, USA.ORCID http://orcid.org/0000-0002-0275-9673
Chih-Hung ChangDepartment of Orthopedic Surgery, Far Eastern Memorial Hospital, New Taipei City, 220216, Taiwan.ORCID http://orcid.org/0000-0002-6992-7176
Andrew S LeeSpot Biosystems Ltd., Palo Alto, CA, 94305, USA.
Yen-Han TsengDepartment of Chest Medicine, Taipei Veterans General Hospital, Taipei, 112201, Taiwan.
Ly James LeeInstitute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan. lee.31@osu.edu.
Hsiu-Jung LiaoInstitute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan. liaohsiujung@gmail.com.ORCID http://orcid.org/0000-0002-1763-6537
Hon-Kan YipDivision of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan. han.gung@msa.hinet.net.
Chi-Ying F HuangInstitute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan. cyhuang5@nycu.edu.tw.ORCID http://orcid.org/0000-0003-4898-4937
National Yang Ming Chiao Tung University · TWAsia University · TWChang Gung University · TWFar Eastern Memorial Hospital · TWKaohsiung Medical University · TWNational Taiwan University · TWOracle (United States) · USTaipei Veterans General Hospital · TWThe Ohio State University · US

Funding

Ministry of Education 112W31101National Science and Technology Council 110-2314-B182A-112-MY3National Science and Technology Council 111-2314-B-075-080National Science and Technology Council 111-2321-B-A49-007National Science and Technology Council 112-2314-B-A49-035National Science and Technology Council 112-2321-B-418-004Veterans General Hospitals and University System of Taiwan Joint Research Program VGHUST112-G1-1-2Yen Tjing Ling Medical Foundation CI-110-3
6 · The paper itself

Abstract

backgroundAcute lung injury (ALI) is a life-threatening respiratory condition characterized by severe inflammation and lung tissue damage, frequently causing rapid respiratory failure and long-term complications. The microRNA let-7a-5p is involved in the progression of lung injury, inflammation, and fibrosis by regulating immune cell activation and cytokine production. This study aims to use an innovative cellular electroporation platform to generate extracellular vesicles (EVs) carring let-7a-5p (EV-let-7a-5p) derived from transfected Wharton's jelly-mesenchymal stem cells (WJ-MSCs) as a potential gene therapy for ALI.

methodsA cellular nanoporation (CNP) method was used to induce the production and release of EV-let-7a-5p from WJ-MSCs transfected with the relevant plasmid DNA. EV-let-7a-5p in the conditioned medium were isolated using a tangential flow filtration (TFF) system. EV characterization followed the minimal consensus guidelines outlined by the International Society for Extracellular Vesicles. We conducted a thorough set of therapeutic assessments, including the antifibrotic effects using a transforming growth factor beta (TGF-β)-induced cell model, the modulation effects on macrophage polarization, and the influence of EV-let-7a-5p in a rat model of hyperoxia-induced ALI.

resultsThe CNP platform significantly increased EV secretion from transfected WJ-MSCs, and the encapsulated let-7a-5p in engineered EVs was markedly higher than that in untreated WJ-MSCs. These EV-let-7a-5p did not influence cell proliferation and effectively mitigated the TGF-β-induced fibrotic phenotype by downregulating SMAD2/3 phosphorylation in LL29 cells. Furthermore, EV-let-7a-5p regulated M2-like macrophage activation in an inflammatory microenvironment and significantly induced interleukin (IL)-10 secretion, demonstrating their modulatory effect on inflammation. Administering EVs from untreated WJ-MSCs slightly improved lung function and increased let-7a-5p expression in plasma in the hyperoxia-induced ALI rat model. In comparison, EV-let-7a-5p significantly reduced macrophage infiltration and collagen deposition while increasing IL-10 expression, causing a substantial improvement in lung function.

conclusionThis study reveals that the use of the CNP platform to stimulate and transfect WJ-MSCs could generate an abundance of let-7a-5p-enriched EVs, which underscores the therapeutic potential in countering inflammatory responses, fibrotic activation, and hyperoxia-induced lung injury. These results provide potential avenues for developing innovative therapeutic approaches for more effective interventions in ALI.

Indexed as

Acute Lung InjuryExtracellular VesiclesHyperoxiaMicroRNAsAnimalsCells, CulturedFibrosisInflammationRatsTransforming Growth Factor betaMicroRNAsTransforming Growth Factor betaAcute lung injuryAnti-inflammationCellular nanoporationExtracellular vesiclesLet-7a-5pMesenchymal stem cells

Identifiers

PMID38500170
PMCPMC10949767
OpenAlexW4392964067

What OpenQuestion 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 OpenQuestion graph.