Stem Cell and EV/sEV Strategies for Neuroimmune Niche Reprogramming in Selected CNS Disorders: Mechanisms, Engineered Delivery, and Translational Readiness.
- 1The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan, China.
Abstract
Background
Aging has traditionally been interpreted through the accumulation of oxidative damage. However, reactive oxygen species (ROS) also act as regulated signals that support immune activation, metabolic adaptation, stress resistance, inflammatory resolution, and cell-fate decisions. We define redox signaling fidelity as the accuracy with which a specified physiological input is converted into a source-specific, spatially confined, temporally patterned, chemically reversible, proportionately decoded, and appropriately resolved redox response.Methods
This critical narrative review develops redox signaling fidelity as a testable systems framework rather than as a synonym for oxidative stress, redox homeostasis, oxidative eustress, hormesis, the redox code, or Redox-stress Response Capacity. The framework organizes redox information flow into five linked layers: generation, encoding, transmission, decoding, and resolution/reset. Aging may lower fidelity through source uncoupling, persistent cysteine oxidation, microdomain leakage, decoder bias, and defective autophagic, mitophagic, lysosomal, or proteostatic reset. Immune aging and the aging brain are used as cross-scale test cases in which physiological ROS pulses must be distinguished from chronic redox noise. We propose operational readouts, including source coupling, redox signal-to-noise ratio, reversibility, spatial leakage, decoder proportionality, mutual information, and resolution kinetics, and map these readouts to single-cell imaging, redox proteomics, spatial and single-cell omics, and dynamic modeling.Conclusions
The fidelity framework predicts that lowering bulk ROS is not sufficient to restore redox function. More decisive studies should pair controlled inputs with compartment-resolved redox dynamics, reversible molecular encoding, pathway output, and functional recovery in the same young-versus-aged system. Interventions should be evaluated by whether they reduce pathological redox noise while preserving physiological pulses, spatial routing, adaptive decoding, and timely resolution.
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BibTeX
@article{lu2026stem,
title = {{Stem Cell and EV/sEV Strategies for Neuroimmune Niche Reprogramming in Selected CNS Disorders: Mechanisms, Engineered Delivery, and Translational Readiness.}},
author = {Wenjing Lu and Junqiang Yan and Hongfang Feng},
journal = {CNS neuroscience \& therapeutics},
year = {2026},
month = oct,
doi = {10.1002/cns.71211},
url = {https://europepmc.org/article/MED/42904805},
note = {CC BY},
}
RIS
TY - JOUR
TI - Stem Cell and EV/sEV Strategies for Neuroimmune Niche Reprogramming in Selected CNS Disorders: Mechanisms, Engineered Delivery, and Translational Readiness.
AU - Wenjing Lu
AU - Junqiang Yan
AU - Hongfang Feng
PY - 2026
DA - 2026/10/01
JO - CNS neuroscience & therapeutics
DO - 10.1002/cns.71211
UR - https://europepmc.org/article/MED/42904805
AB - Background Aging has traditionally been interpreted through the accumulation of oxidative damage. However, reactive oxygen species (ROS) also act as regulated signals that support immune activation, metabolic adaptation, stress resistance, inflammatory resolution, and cell-fate decisions. We define redox signaling fidelity as the accuracy with which a specified physiological input is converted into a source-specific, spatially confined, temporally patterned, chemically reversible, proportionately decoded, and appropriately resolved redox response.Methods This critical narrative review develops redox signaling fidelity as a testable systems framework rather than as a synonym for oxidative stress, redox homeostasis, oxidative eustress, hormesis, the redox code, or Redox-stress Response Capacity. The framework organizes redox information flow into five linked layers: generation, encoding, transmission, decoding, and resolution/reset. Aging may lower fidelity through source uncoupling, persistent cysteine oxidation, microdomain leakage, decoder bias, and defective autophagic, mitophagic, lysosomal, or proteostatic reset. Immune aging and the aging brain are used as cross-scale test cases in which physiological ROS pulses must be distinguished from chronic redox noise. We propose operational readouts, including source coupling, redox signal-to-noise ratio, reversibility, spatial leakage, decoder proportionality, mutual information, and resolution kinetics, and map these readouts to single-cell imaging, redox proteomics, spatial and single-cell omics, and dynamic modeling.Conclusions The fidelity framework predicts that lowering bulk ROS is not sufficient to restore redox function. More decisive studies should pair controlled inputs with compartment-resolved redox dynamics, reversible molecular encoding, pathway output, and functional recovery in the same young-versus-aged system. Interventions should be evaluated by whether they reduce pathological redox noise while preserving physiological pulses, spatial routing, adaptive decoding, and timely resolution.
SN - 1755-5930
SN - 1755-5949
ER -