Evidence map›Paper›PMID 41526541›Full record

ArticleInflammation2026

TSG-6 Activated MSC-derived Extracellular Vesicles Present Altered micro-RNA Contents and Ameliorate the Inflammatory Phenotype of Macrophages in Vitro.

Iker Martinez-Zalbidea, Alyssa Rzasa, Varun Puvanesarajah, Wolfgang Hitzl, Karin Wuertz-Kozak

Abstract read
In one paragraph

Article in Inflammation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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. Review
  4. Recent advances in biomarkers for cardiac fibrosis.Frontiers in cardiovascular medicine · 2026
    Review
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

5 authors.

Iker Martinez-ZalbideaDepartment of Biomedical Engineering, Rochester Institute of Technology (RIT), Rochester, NY, USA.
Alyssa RzasaDepartment of Biomedical Engineering, Rochester Institute of Technology (RIT), Rochester, NY, USA.
Varun PuvanesarajahDepartment of Orthopedics and Rehabilitation, University of Rochester Medical Center, Rochester, NY, USA.
Wolfgang HitzlResearch and Innovation Management (RIM), Paracelsus Medical University, Salzburg, Austria.
Karin Wuertz-KozakDepartment of Biomedical Engineering, Rochester Institute of Technology (RIT), Rochester, NY, USA. kwbme@rit.edu.

Funding

Extracellular vesicles produced by CRISPR-activated MSCs: A potential therapy for degenerative disc diseaseR21AR081987 · NIAMS · ROCHESTER INSTITUTE OF TECHNOLOGY · PI WUERTZ-KOZAK, KARIN · 2023 to 2024
$365k
National Science Foundation 2229111NIAMS NIH HHS 1R21AR081987-01A1NIAMS NIH HHS R21 AR081987
6 · The paper itself

Abstract

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have shown promising immunomodulatory properties; however, strategies to enhance their therapeutic potential remain limited. Here, we employed CRISPR activation of the gene TSG-6 in MSCs to evaluate the impact of elevated TSG-6 on EV cargo and immunomodulatory function in an in vitro macrophage model. CRISPR-mediated gene activation was confirmed by RT-qPCR, demonstrating more than an 1800 fold increase in TSG-6 mRNA compared to controls. EVs were isolated from TSG-6 overexpressing MSCs and thoroughly characterized by nanoparticle tracking analysis, transmission electron microscopy, and Western blot, confirming their typical size distribution, morphology, and surface markers. Small RNA sequencing of these EVs revealed 15 differentially expressed miRNAs relative to EVs from control MSCs. When THP-1-derived macrophages were stimulated with LPS and treated with TSG-6-overexpressing MSC-EVs (Standard dosage: 1000 particle/cell, n = 11; Alternative dosages: 500, 1000, or 2000 particles/cell, n = 6), a marked reduction in pro-inflammatory cytokine gene expression (IL-1β, CCL2, CXCL10, and TNF-α) and secreted protein levels (CCL2, TNF-α, CXCL1, and MIP-3α) was observed. Taken together, these findings demonstrate that CRISPR-based TSG-6 activation reprograms MSC-EV miRNA cargo (as well as their protein cargo, as previously shown), which can boost their anti-inflammatory effects. These findings underscore the promise of CRISPR-activation as a novel platform for boosting the bioactive properties of MSC-EVs and enhancing immunotherapeutic efficacy.

Indexed as

Cell Adhesion MoleculesExtracellular VesiclesInflammationMacrophagesMesenchymal Stem CellsMicroRNAsCytokinesHumansPhenotypeTHP-1 CellsCell Adhesion MoleculesCytokinesMicroRNAsTNFAIP6 protein, humanExtracellular vesiclesMacrophage, polarizationMesenchymal stem cellsMicro-RNATranscriptomic modulation

Identifiers

PMID41526541
PMCPMC12862027

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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.