Evidence map›Paper›PMID 36122169›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2023

Role of Human Mesenchymal Stem Cells and Derived Extracellular Vesicles in Reducing Sensory Neuron Hyperexcitability and Pain Behaviors in Murine Osteoarthritis.

Minji Ai, William E Hotham, Luke A Pattison, Qingxi Ma, Frances M D Henson, Ewan St John Smith

Open access · hybridAbstract read
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 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

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.

  1. Pooled it
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  12. Not Just Neurons: Pain Is Orchestrated in Partnership with Many Non-neuronal Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Review
  13. Article
  14. Artemin sensitises mouse (Mus musculus) and naked mole-rat (Heterocephalus glaber) sensory neurons in vitro.Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology · 2025
    Article
  15. Article
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  18. Emerging Therapy in Osteoarthritis: Mesenchymal Stem Cells, Secretomes, and Using Hydrogels to Enhance Efficacy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025
    Review
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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

6 authors at 1 institution in 1 country.

Minji AiDepartment of Veterinary Medicine, University of Cambridge, UK.
William E HothamDepartment of Surgery and Department of Medicine, University of Cambridge, UK.
Luke A PattisonDepartment of Pharmacology, University of Cambridge, UK.
Qingxi MaDepartment of Pharmacology, University of Cambridge, UK.
Frances M D HensonDepartment of Surgery, University of Cambridge, UK.
Ewan St John SmithDepartment of Pharmacology, University of Cambridge, UK.ORCID 0000-0002-2699-1979
University of Cambridge · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveMesenchymal stem/stromal cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) have been reported to alleviate pain in patients with knee osteoarthritis (OA). We undertook this study to determine whether MSCs and/or MSC-EVs reduce OA pain through influencing sensory neuron excitability in OA joints.

methodsWe induced knee OA in adult male C57BL/6J mice through destabilization of the medial meniscus (DMM) surgery. Mice were sorted into 4 experimental groups with 9 mice per group as follows: unoperated sham, untreated DMM, DMM plus MSC treatment, and DMM plus MSC-EV treatment. Treated mice received either MSCs at week 14 postsurgery or MSC-EVs at weeks 12 and 14 postsurgery. Mouse behavior was evaluated by digging and rotarod tests and the Digital Ventilated Cage system. At week 16, mouse knee joints were harvested for histology, and dorsal root ganglion (DRG) neurons were isolated for electrophysiology. Furthermore, we induced hyperexcitability in DRG neurons in vitro using nerve growth factor (NGF) then treated these neurons with or without MSC-EVs and evaluated neuron excitability.

resultsMSC- and MSC-EV-treated DMM-operated mice did not display pain-related behavior changes (in locomotion, digging, and sleep) that occurred in untreated DMM-operated mice. The absence of pain-related behaviors in MSC- and MSC-EV-treated mice was not the result of reduced joint damage but rather a lack of knee-innervating sensory neuron hyperexcitability that was observed in untreated DMM-operated mice. Furthermore, we found that NGF-induced sensory neuron hyperexcitability is prevented by MSC-EV treatment (P < 0.05 versus untreated NGF-sensitized neurons when comparing action potential threshold).

conclusionMSCs and MSC-EVs may reduce pain in OA by direct action on peripheral sensory neurons.

Indexed as

Extracellular VesiclesOsteoarthritis, KneeAdultAnimalsHumansMaleMiceMice, Inbred C57BLNerve Growth FactorPainSensory Receptor CellsNerve Growth Factor

Identifiers

PMID36122169
PMCPMC10952633
OpenAlexW4296458933

What OpenQuestion holds

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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.