Evidence map›Paper›PMID 34724347›Full record

ArticleJournal of extracellular vesicles2021

Reversing the surface charge of MSC-derived small extracellular vesicles by εPL-PEG-DSPE for enhanced osteoarthritis treatment.

Kai Feng, Xuetao Xie, Ji Yuan, Liangzhi Gong, Zhaochen Zhu, Juntao Zhang, Haiyan Li, Yunlong Yang, Yang Wang

Open access · goldAbstract read
In one paragraph

Article in Journal of extracellular vesicles, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 2 pooled it
5.4field-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

68 citing papers in PubMed, 2 syntheses or guidelines pooled it, 106 citations in OpenAlex.

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  20. Extracellular vesicles ofGut microbes · 2025
    Article

8 more citing papers are in PubMed but not listed here.

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

9 authors at 3 institutions in 2 countries.

Kai FengInstitute of Microsurgery on Extremities, Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Xuetao XieInstitute of Microsurgery on Extremities, Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Ji YuanInstitute of Microsurgery on Extremities, Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Liangzhi GongInstitute of Microsurgery on Extremities, Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Zhaochen ZhuInstitute of Microsurgery on Extremities, Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Juntao ZhangInstitute of Microsurgery on Extremities, Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Haiyan LiChemical and Environmental Engineering, School of Engineering, RMIT University, Melbourne, Australia.
Yunlong YangInstitute of Microsurgery on Extremities, Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Yang WangInstitute of Microsurgery on Extremities, Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Shanghai Jiao Tong University · CNShanghai Sixth People's Hospital · CNRMIT University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) possess a great therapeutical potential for osteoarthritis (OA) treatment. However, the steric and electrostatic hindrance of cartilage matrix leads to very limited distribution of MSC-sEVs in cartilage and low bioavailability of MSC-sEVs after intra-articular injection. To overcome this, a strategy to reverse the surface charge of MSC-sEVs by modifying the MSC-sEVs with a novel cationic amphiphilic macromolecule namely ε-polylysine-polyethylene-distearyl phosphatidylethanolamine (PPD) was developed in this study. Through incubation with 100 μg/ml PPD, positively charged MSC-sEVs (PPD-sEVs) were obtained, and the modification process showed nearly no disturbance to the integrity and contents of sEVs and exhibited good stability under the interference of anionic macromolecules. A more effective cellular uptake and homeostasis modulation ability of PPD-sEVs than unmodified MSC-sEVs to chondrocytes was demonstrated. More importantly, PPD-sEVs demonstrated significantly enhanced cartilage uptake, cartilage penetration, and joint retention capacity as compared to MSC-sEVs. Intra-articular injection of PPD-sEVs into a mouse OA model showed significantly improved bioavailability than MSC-sEVs, which resulted in enhanced therapeutic efficacy with reduced injection frequency. In general, this study provides a facile and effective strategy to improve the intra-articular bioavailability of MSC-sEVs and has a great potential to accelerate the clinical practice of MSC-sEVs based OA therapy.

Indexed as

AdolescentAnimalsCartilageCell- and Tissue-Based TherapyCells, CulturedChondrocytesDisease Models, AnimalExtracellular VesiclesHumansInduced Pluripotent Stem CellsInjections, Intra-ArticularMaleMesenchymal Stem CellsMiceMice, Inbred C57BLOsteoarthritis1,2-dioleoyl-3-phosphoethanolamine-n-(poly(ethyleneglycol))-hydroxy succinamidePhosphatidylethanolaminespolyethylene glycol-distearoylphosphatidylethanolaminePolyethylene GlycolsPolylysineMSC derived small extracellular vesiclesosteoarthritissurface charge reversesurface modification

Identifiers

PMID34724347
PMCPMC8559985
OpenAlexW3210302313

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.