Extracellular vesicles reprogram cytokine signaling and the immune microenvironment in intervertebral disc degeneration
- 1Department of Orthopedics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- 2Department of Neurosurgery, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China
Abstract
Intervertebral disc degeneration (IVDD) involves matrix failure and communication between disc-resident and infiltrating immune cells. Mechanical, metabolic and inflammatory stress can alter recipient-cell states through extracellular vesicle (EV) communication and soluble cytokine signaling. We review how donor-cell conditions affect EV cargo, how recipient cells respond and how these responses affect disc injury and repair. Among the endogenous EV pathways reviewed, communication between nucleus pulposus (NP) cells and macrophages has the strongest support. Degenerative disc-cell EVs promote inflammatory macrophage responses, while macrophage small EVs reinforce NP-cell senescence, inflammatory secretion and matrix catabolism. A complete feedback loop has not been demonstrated in native human discs. Therapeutic preparations from mesenchymal stromal cells, conditioned macrophages and platelet products can restrain inflammatory signaling and restore autophagy, mitochondrial function and extracellular matrix synthesis in preclinical models. These effects do not establish whole-disc regeneration or clinical pain relief. Evidence that EVs regulate cytokine production or responsiveness is stronger than evidence that cytokines are physically carried by EVs; the latter requires localization and vesicle-dependent functional controls. Clinical development requires reproducible EV identity and purity and potency assays that reflect the proposed mechanism. Sustained local exposure, biodistribution and safety also need evaluation. Structural repair, immune modulation and pain relief should be assessed separately.
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BibTeX
@article{duan2026extracellular,
title = {{Extracellular vesicles reprogram cytokine signaling and the immune microenvironment in intervertebral disc degeneration}},
author = {Yuchen Duan and Fei Yang and Yi Zhou and Rigao Chen and Wenjie Liu},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1997468},
url = {https://doi.org/10.3389/fimmu.2026.1997468},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Extracellular vesicles reprogram cytokine signaling and the immune microenvironment in intervertebral disc degeneration
AU - Yuchen Duan
AU - Fei Yang
AU - Yi Zhou
AU - Rigao Chen
AU - Wenjie Liu
PY - 2026
DA - 2026/11/04
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1997468
UR - https://doi.org/10.3389/fimmu.2026.1997468
AB - Intervertebral disc degeneration (IVDD) involves matrix failure and communication between disc-resident and infiltrating immune cells. Mechanical, metabolic and inflammatory stress can alter recipient-cell states through extracellular vesicle (EV) communication and soluble cytokine signaling. We review how donor-cell conditions affect EV cargo, how recipient cells respond and how these responses affect disc injury and repair. Among the endogenous EV pathways reviewed, communication between nucleus pulposus (NP) cells and macrophages has the strongest support. Degenerative disc-cell EVs promote inflammatory macrophage responses, while macrophage small EVs reinforce NP-cell senescence, inflammatory secretion and matrix catabolism. A complete feedback loop has not been demonstrated in native human discs. Therapeutic preparations from mesenchymal stromal cells, conditioned macrophages and platelet products can restrain inflammatory signaling and restore autophagy, mitochondrial function and extracellular matrix synthesis in preclinical models. These effects do not establish whole-disc regeneration or clinical pain relief. Evidence that EVs regulate cytokine production or responsiveness is stronger than evidence that cytokines are physically carried by EVs; the latter requires localization and vesicle-dependent functional controls. Clinical development requires reproducible EV identity and purity and potency assays that reflect the proposed mechanism. Sustained local exposure, biodistribution and safety also need evaluation. Structural repair, immune modulation and pain relief should be assessed separately.
SN - 1664-3224
ER -