Evidence map›Paper›PMID 40001168›Full record

ArticleJournal of nanobiotechnology2025

MSCs-EVs harboring OA immune memory reprogram macrophage phenotype via modulation of the mt-ND3/NADH-CoQ axis for OA treatment.

Jingdi Zhan, Jing Zou, Qiming Pang, Zhuolin Chen, Junyan Liu, Senrui Liu, Chengcheng Du, Jiacheng Liu, Weikang Zhao, Lili Dong and 1 more

Abstract read
In one paragraph

Article in Journal of nanobiotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
–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

15 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

11 authors.

Jingdi ZhanDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Jing ZouDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Qiming PangDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Zhuolin ChenDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Junyan LiuDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Senrui LiuDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Chengcheng DuDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Jiacheng LiuDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Weikang ZhaoDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. weikangzhao90@hospital.cqmu.edu.cn.
Lili DongDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. dllbme@alu.cqu.edu.cn.
Wei HuangDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. huangwei68@263.net.

Funding

China Natural Science Foundation 82102571China Postdoctoral Science Foundation 2022M710564Doctoral Innovation Project of the First Affiliated Hospital of Chongqing Medical University CYYY-BSYJSCXXM-202308National Natural Science Foundation of China-Joint Fund Project U22A20284Natural Science Foundation of Chongqing, China CSTB2022NSCQ-BHX0683Postdoctoral Special Funding Project of Chongqing Human Resources and Social Security Bureau 2112012726787861
6 · The paper itself

Abstract

backgroundOsteoarthritis (OA) is a prevalent degenerative joint disease and current therapies are insufficient to halt its progression. Mesenchymal stem cells-derived extracellular vesicles (MSCs-EVs) offer promising therapeutic potential for OA treatment, and their efficacy can be enhanced through strategic engineering approaches.

methodsInspired by the immune memory of the adaptive immune system, we developed an engineered strategy to impart OA-specific immune memory to MSCs-EVs. Using Luminex technology, inflammatory factors (IFN-γ, IL-6, and TNF-α), which mimic the OA inflammatory microenvironment, were identified and used to prime MSCs, generating immune memory-bearing MSCs-EVs (iEVs). Proteomic analysis and complementary experiments were conducted to evaluate iEVs' effects on macrophage phenotypic reprogramming.

resultsiEVs, particularly IL-6-EV, exhibited potent immunoregulatory functions along with the ability to modulate mitochondrial metabolism. Both in vitro and in vivo, IL-6-EV significantly reprogrammed macrophages towards the M2 subtype, effectively suppressing articular inflammation and OA progression. Mechanistic studies revealed that IL-6-EV facilitated M2 polarization by regulating mitochondrial oxidative phosphorylation via the mt-ND3/NADH-CoQ axis.

conclusionThis study introduces a strategy to enhance MSCs-EVs' therapeutic efficacy in OA. Multi-omics analysis and biological validation demonstrate its potential, providing new insights for MSCs-EVs' future application in OA and other clinical conditions.

Indexed as

Extracellular VesiclesImmunologic MemoryMacrophagesMesenchymal Stem CellsOsteoarthritisAnimalsHumansInterleukin-6MaleMiceMice, Inbred C57BLMitochondriaPhenotypeRAW 264.7 CellsInterleukin-6EngineeredMacrophagesMitochondria metabolismMSCs-derived extracellular vesiclesmt-ND3Osteoarthritis

Identifiers

PMID40001168
PMCPMC11863759

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.