Extracellular Vesicles in the Mesenchymal Stem Cell/Macrophage Axis: Potential Targets for Inflammatory Treatment
Abstract
1. Introduction
2. Basis of the Interaction Between MSCs and Mφ
2.1. Dual Roles of Mφ
2.2. Biological Characteristics of MSCs
2.3. Classical Mechanisms of MSCs Regulating Mφ Polarization
3. Biological Characteristics and Functions of EVs
3.1. Classification and Biogenesis of EVs
3.2. Intercellular Communication Mechanisms of EVs
4. Mechanisms of EVs Mediating the MSC/Mφ Axis Regulating Inflammation
4.1. Key Molecules in Contents of EVs
4.2. Signaling Pathway Regulation
4.2.1. TLR/MyD88/NF-κB Signaling Pathway
4.2.2. PI3K/Akt/mTOR Signaling Pathway
4.2.3. STAT Signaling Pathway
4.3. Microenvironment Remodeling Effect
5. Advanced Experimental and Clinical Studies of EVs in Inflammatory Diseases
5.1. Evidence from Different IMID Models
5.2. Clinical Transformation Progress
6. Challenges and Future Prospects
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
SYSU | Sun Yat-Sen University |
EVs | Extracellular vesicles (EVs) |
MSCs | Mesenchymal stem cells |
Mφ | Macrophages |
MSC/Mφ axis | Mesenchymal stem cells/macrophages axis |
RA | Rheumatoid arthritis |
IBD | Inflammatory bowel disease |
M1φ | M1-like macrophages |
M2φ | M2-like macrophages |
MSC-EVs | Mesenchymal stem cell-derived EVs |
Mφ-EVs | Macrophage-derived EVs |
UC-MSCs | Umbilical cord mesenchymal stem cells |
AMSCs | Amniotic mesenchymal stem cells |
BM-MSCs | Bone marrow mesenchymal stem cells |
AD-MSCs | Adipose tissue mesenchymal stem cells |
TLRs | Toll-like receptors |
PAMPs | Pathogen-associated molecular patterns |
DAMPs | Damage-associated molecular patterns |
LPS | Lipopolysaccharide |
HMGB1 | High-mobility group box 1 protein |
NF-κB | Nuclear factor kappa-light-chain-enhancer of activated B cells |
Bregs | Regulatory B cells |
IRF5 | Interferon regulatory factor 5 |
STAT1 | Signal transducer and activator of transcription 1 |
iNOS | Inducible nitric oxide synthase |
TNF-α | Tumor necrosis factor α |
IL6 | Interleukin 6 |
CD86 | Cluster of Differentiation 86 |
IRF4 | Interferon regulatory factor 4 |
STAT6 | Signal transducer and activator of transcription 6 |
IL10 | Interleukin 10 |
CD206 | Cluster of Differentiation 206 |
DMARDs | Disease-modifying antirheumatic drugs |
IMIDs | Immune-mediated inflammatory diseases |
TGF-β | Transforming growth factor β |
CD200 | Cluster of Differentiation 200 |
CD200R | Cluster of Differentiation 200 receptors |
HIF-1α | Hypoxia-inducible factor 1α |
miRNAs | Micro-RNAs |
miR-223 | MicroRNA-223 |
PKNOX1 | PBX/Knotted 1 Homeobox 1 |
miR-181c | MicroRNA-181c |
TLR4 | Toll-like receptor 4 |
miR-21 | MicroRNA-21 |
PTEN | Phosphatase and tensin homolog |
Akt | Protein kinase B |
BBB | Blood–brain barrier |
MVs | Microvesicles |
ApoVs | Apoptotic vesicles |
lncRNA | Long non-coding RNA |
CD9 | Cluster of Differentiation 9 |
CD81 | Cluster of Differentiation 81 |
FasL | Fas ligand |
MHC | Major histocompatibility complex |
Tregs | Regulatory T cells |
miR-155-3p | MicroRNA-155-3p |
miR-148a-3p | MicroRNA-148a-3p |
miR-1a-3p | MicroRNA-1a-3p |
miR-143-3p | MicroRNA-143-3p |
STAT3 | Signal transducer and activator of transcription 3 |
JNK | c-Jun N-terminal kinase |
miR-709 | MicroRNA-709 |
M2φ-EVs | M2-like macrophages-derived EVs |
ALI | Acute lung injury |
ARDS | Acute respiratory distress syndrome |
IL-1β | Interleukin 1β |
NLRP3 | NLR family pyrin domain-containing 3 |
PD | Periodontitis |
Pg | Porphyromonas gingivalis |
miR-143-3p | MicroRNA-143-3p |
IGFBP5 | Insulin-like growth factor-binding protein 5 |
miR-92a-3p | MicroRNA-92a-3p |
SOST | Sclerostin |
miR-625-3p | MicroRNA-625-3p |
miR-671-5p | MicroRNA-671-5p |
AAK1 | Adaptor-associated protein kinase 1 |
TSG6 | Tumor necrosis factor-inducible gene 6 protein |
TLR2 | Toll-like receptor 2 |
CD44 | Cluster of Differentiation 44 |
IFN-γ | Interferon gamma |
JAK | Janus kinase |
COX-2 | Cyclooxygenase-2 |
cAMP | Cyclic adenosine monophosphate |
PKA | Protein kinase A |
IL12 | Interleukin 12 |
LDHA | Lactate dehydrogenase |
PKM2 | Pyruvate kinase M2 |
MyD88 | Myeloid differentiation primary response 88 |
miR-146a | MicroRNA-146a |
UTR | Untranslated region |
mRNA | Messenger RNA |
IL-1R | Interleukin-1 receptor |
IRAK | IL-1R-associated kinase |
IκBα | Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha |
SOD2 | Superoxide dismutase 2 |
ROS | Reactive oxygen species |
IKK | IκB kinase |
PI3K | Phosphatidylinositol 3-kinase (PI3K) |
PIP3 | Phosphatidylinositol-3,4,5-triphosphate |
mTOR | Mammalian target of rapamycin |
mTORC1 | mTOR complex 1 |
TSC1 | Tuberous sclerosis complex 1 |
TSC2 | Tuberous sclerosis complex 2 |
FAO | Fatty acid oxidation |
PGC-1α | Peroxisome proliferator-activated receptor gamma coactivator 1-alpha |
OXPHOS | Oxidative phosphorylation |
IL4 | Interleukin 4 |
IL13 | Interleukin 13 |
JAK1 | Janus kinase 1 |
JAK3 | Janus kinase 3 |
IL-4Rα | Interleukin 4 receptor α |
SOCS | Suppressor of cytokine signaling |
PPARγ | Peroxisome proliferator-activated receptor γ |
IL18 | Interleukin 18 |
AD | Atopic dermatitis |
CA-EVs | Curcumin–albumin-EVs |
dMNAs | Dissolvable microneedle arrays |
VCAM1 | Vascular cell adhesion molecule 1 |
ITGA4 | Integrin subunit alpha 4 |
SARS-CoV-2 | Coronavirus 2 |
COPD | Chronic obstructive pulmonary disease |
SOCS3 | Suppressor of cytokine signaling-3 |
BAL | Bronchoalveolar lavage |
OA | Osteoarthritis |
SASP | Senescence-associated secretory phenotype |
BCC | Bioorthogonal copper-free click chemistry |
MGE | Metabolic glycoengineering |
O-EVs | Orally administered EVs |
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Che, Z.; Yan, W.; Zhao, Q. Extracellular Vesicles in the Mesenchymal Stem Cell/Macrophage Axis: Potential Targets for Inflammatory Treatment. Int. J. Mol. Sci. 2025, 26, 2827. https://doi.org/10.3390/ijms26062827
Che Z, Yan W, Zhao Q. Extracellular Vesicles in the Mesenchymal Stem Cell/Macrophage Axis: Potential Targets for Inflammatory Treatment. International Journal of Molecular Sciences. 2025; 26(6):2827. https://doi.org/10.3390/ijms26062827
Chicago/Turabian StyleChe, Zhen, Wenbin Yan, and Qun Zhao. 2025. "Extracellular Vesicles in the Mesenchymal Stem Cell/Macrophage Axis: Potential Targets for Inflammatory Treatment" International Journal of Molecular Sciences 26, no. 6: 2827. https://doi.org/10.3390/ijms26062827
APA StyleChe, Z., Yan, W., & Zhao, Q. (2025). Extracellular Vesicles in the Mesenchymal Stem Cell/Macrophage Axis: Potential Targets for Inflammatory Treatment. International Journal of Molecular Sciences, 26(6), 2827. https://doi.org/10.3390/ijms26062827