Evidence map›Paper›PMID 38534328›Full record

ArticleCells2024

Modification of Mesenchymal Stem/Stromal Cell-Derived Small Extracellular Vesicles by Calcitonin Gene Related Peptide (CGRP) Antagonist: Potential Implications for Inflammation and Pain Reversal.

Kevin Liebmann, Mario A Castillo, Stanislava Jergova, Thomas M Best, Jacqueline Sagen, Dimitrios Kouroupis

Open access · goldAbstract read
In one paragraph

Article in Cells, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
5.6field-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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Pooled it
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  14. Human mesenchymal stem/stromal cell-derived extracellular vesicle transport in meniscus fibrocartilage.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2025
    Article
  15. Article
  16. Review
  17. Article
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  19. Engineered Extracellular Vesicles in Arthritic Diseases: Therapeutic Applications & Challenges.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology
    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

6 authors at 2 institutions in 1 country.

Kevin LiebmannDepartment of Orthopedics, UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, FL 33146, USA.
Mario A CastilloDepartment of Orthopedics, UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, FL 33146, USA.
Stanislava JergovaMiami Project to Cure Paralysis, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.ORCID 0000-0002-9096-7770
Thomas M BestDepartment of Orthopedics, UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, FL 33146, USA.
Jacqueline SagenMiami Project to Cure Paralysis, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.ORCID 0000-0002-9742-7240
Dimitrios KouroupisDepartment of Orthopedics, UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, FL 33146, USA.ORCID 0000-0002-3892-9013
University of Miami · USUniversity of Miami Health System · US

Funding

CD10-bound Exosomes from IFP-MSC Degrade Substance P Controlling OA Inflammation and PainR21AR080388 · NIAMS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI KOUROUPIS, DIMITRIOS · 2022 to 2023
$371k
NIAMS NIH HHS R21 AR080388NIH HHS 5R21AR080388-02
6 · The paper itself

Abstract

During the progression of knee osteoarthritis (OA), the synovium and infrapatellar fat pad (IFP) can serve as source for Substance P (SP) and calcitonin gene-related peptide (CGRP), two important pain-transmitting, immune, and inflammation modulating neuropeptides. Our previous studies showed that infrapatellar fat pad-derived mesenchymal stem/stromal cells (MSC) acquire a potent immunomodulatory phenotype and actively degrade Substance P via CD10 both in vitro and in vivo. On this basis, our hypothesis is that CD10-bound IFP-MSC sEVs can be engineered to target CGRP while retaining their anti-inflammatory phenotype. Herein, human IFP-MSC cultures were transduced with an adeno-associated virus (AAV) vector carrying a GFP-labelled gene for a CGRP antagonist peptide (aCGRP). The GFP positive aCGRP IFP-MSC were isolated and their sEVs' miRNA and protein cargos were assessed using multiplex methods. Our results showed that purified aCGRP IFP-MSC cultures yielded sEVs with cargo of 147 distinct MSC-related miRNAs. Reactome analysis of miRNAs detected in these sEVs revealed strong involvement in the regulation of target genes involved in pathways that control pain, inflammation and cartilage homeostasis. Protein array of the sEVs cargo demonstrated high presence of key immunomodulatory and reparative proteins. Stimulated macrophages exposed to aCGRP IFP-MSC sEVs demonstrated a switch towards an alternate M2 status. Also, stimulated cortical neurons exposed to aCGRP IFP-MSC sEVs modulate their molecular pain signaling profile. Collectively, our data suggest that yielded sEVs can putatively target CGRP in vivo, while containing potent anti-inflammatory and analgesic cargo, suggesting the promise for novel sEVs-based therapeutic approaches to diseases such as OA.

Indexed as

Extracellular VesiclesMicroRNAsAnti-Inflammatory AgentsCalcitonin Gene-Related PeptideHumansInflammationPainStromal CellsSubstance PAnti-Inflammatory AgentsCalcitonin Gene-Related PeptideMicroRNAsSubstance Panalgesiacalcitonin gene-related peptide (CGRP)CD10 (neprilysin)immunomodulationinfrapatellar fat pad (IFP)mesenchymal stem/stromal cells (MSC)osteoarthritis (OA)small extracellular vesicles (sEVs)synovium

Identifiers

PMID38534328
PMCPMC10969778
OpenAlexW4392659719

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.