Evidence map›Paper›PMID 30922413›Full record

ArticleStem cell research & therapy2019

Interaction with hyaluronan matrix and miRNA cargo as contributors for in vitro potential of mesenchymal stem cell-derived extracellular vesicles in a model of human osteoarthritic synoviocytes.

Enrico Ragni, Carlotta Perucca Orfei, Paola De Luca, Gaia Lugano, Marco Viganò, Alessandra Colombini, Federico Valli, Daniele Zacchetti, Valentina Bollati, Laura de Girolamo

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 3 pooled it
4.4field-weighted citation impact, top 5% 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

61 citing papers in PubMed, 3 syntheses or guidelines pooled it, 90 citations in OpenAlex.

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  20. Exosomes Derived from E2F1International journal of nanomedicine · 2023
    Article

1 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

10 authors at 3 institutions in 1 country.

Enrico RagniIRCCS Istituto Ortopedico Galeazzi, Laboratorio di Biotecnologie Applicate all'Ortopedia, Milan, Italy. enrico.ragni@grupposandonato.it.ORCID 0000-0003-0272-7417
Carlotta Perucca OrfeiIRCCS Istituto Ortopedico Galeazzi, Laboratorio di Biotecnologie Applicate all'Ortopedia, Milan, Italy.ORCID 0000-0001-6162-8668
Paola De LucaIRCCS Istituto Ortopedico Galeazzi, Laboratorio di Biotecnologie Applicate all'Ortopedia, Milan, Italy.ORCID 0000-0001-9810-8818
Gaia LuganoIRCCS Istituto Ortopedico Galeazzi, Laboratorio di Biotecnologie Applicate all'Ortopedia, Milan, Italy.ORCID 0000-0002-3068-7339
Marco ViganòIRCCS Istituto Ortopedico Galeazzi, Laboratorio di Biotecnologie Applicate all'Ortopedia, Milan, Italy.ORCID 0000-0002-6463-6564
Alessandra ColombiniIRCCS Istituto Ortopedico Galeazzi, Laboratorio di Biotecnologie Applicate all'Ortopedia, Milan, Italy.ORCID 0000-0002-1800-3424
Federico ValliIRCCS Istituto Ortopedico Galeazzi, Chirurgia Articolare Sostitutiva e Chirurgia Ortopedica (CASCO), Milan, Italy.
Daniele ZacchettiDivision of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.ORCID 0000-0003-2724-7559
Valentina BollatiEPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.ORCID 0000-0002-0370-9598
Laura de GirolamoIRCCS Istituto Ortopedico Galeazzi, Laboratorio di Biotecnologie Applicate all'Ortopedia, Milan, Italy.ORCID 0000-0002-9979-3092
Istituto Ortopedico Galeazzi · ITUniversity of Milan · ITVita-Salute San Raffaele University · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOsteoarthritis (OA) is the most prevalent joint disease, and to date, no options for effective tissue repair and restoration are available. With the aim of developing new therapies, the impact of mesenchymal stem cells (MSCs) has been explored, and the efficacy of MSCs started to be deciphered. A strong paracrine capacity relying on both secreted and vesicle-embedded (EVs) protein or nucleic acid-based factors has been proposed as the principal mechanism that contributes to tissue repair. This work investigated the mechanism of internalization of extracellular vesicles (EVs) released by adipose-derived MSCs (ASCs) and the role of shuttled miRNAs in the restoration of homeostasis in an in vitro model of human fibroblast-like synoviocytes (FLSs) from OA patients.

methodsASC-EVs were isolated by differential centrifugation and validated by flow cytometry and nanoparticle tracking analysis. ASC-EVs with increased hyaluronan (HA) receptor CD44 levels were obtained culturing ASCs on HA-coated plastic surfaces. OA FLSs with intact or digested HA matrix were co-cultured with fluorescent ASC-EVs, and incorporation scored by flow cytometry and ELISA. ASC-EV complete miRNome was deciphered by high-throughput screening. In inflamed OA FLSs, genes and pathways potentially regulated by ASC-EV miRNA were predicted by bioinformatics. OA FLSs stimulated with IL-1β at physiological levels (25 pg/mL) were treated with ASC-EVs, and expression of inflammation and OA-related genes was measured by qRT-PCR over a 10-day time frame with modulated candidates verified by ELISA.

resultsThe data showed that HA is involved in ASC-EV internalization in FLSs. Indeed, both removal of HA matrix presence on FLSs and modulation of CD44 levels on EVs affected their recruitment. Bioinformatics analysis of EV-embedded miRNAs showed their ability to potentially regulate the main pathways strictly associated with synovial inflammation in OA. In this frame, ASC-EVs reduced the expression of pro-inflammatory cytokines and chemokines in a chronic model of FLS inflammation.

conclusionsGiven their ability to affect FLS behavior in a model of chronic inflammation through direct interaction with HA matrix and miRNA release, ASC-EVs confirm their role as a novel therapeutic option for osteoarthritic joints.

Indexed as

Extracellular VesiclesModels, BiologicalOsteoarthritisHumansHyaluronic AcidMesenchymal Stem CellsMicroRNAsHyaluronic AcidMicroRNAsAdipose-derived mesenchymal stem cellsExtracellular vesiclesHyaluronan coatmiRNAOsteoarthritisSynoviocytes

Identifiers

PMID30922413
PMCPMC6440078
OpenAlexW2942721638

What OpenQuestion holds

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LicenceCC BY
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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.