Multicompartment Quantitative Proteomics Revealing Potential Mechanisms Underlying the Treatment Effects of Mesenchymal-Derived Extracellular Vesicles in a Monkey Model of Cortical Injury
Recommended Citation
Qian S, McCann RP, Shen S, Zhu X, Tsillas CM, Xin H, Wang M, Zhang Y, Zhang ZG, Chopp M, Medalla M, Moore TL, and Qu J. Multicompartment Quantitative Proteomics Revealing Potential Mechanisms Underlying the Treatment Effects of Mesenchymal-Derived Extracellular Vesicles in a Monkey Model of Cortical Injury. J Proteome Res 2025;24(11):5664-5682.
Document Type
Article
Publication Date
11-7-2025
Publication Title
Journal of proteome research
Keywords
Animals, Extracellular Vesicles, Proteomics, Macaca mulatta, Female, Mesenchymal Stem Cells, Disease Models, Animal, Brain Injuries, Proteome, Motor Cortex
Abstract
Previous studies have demonstrated that mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) enhance functional recovery after cortical injury in rhesus monkeys by reducing chronic microglial inflammation, neuronal damage, and myelination deficits. However, the signaling pathways underlying these therapeutic effects remain largely unexplored. In this study, employing a reliable quantitative proteomics platform UHR-IonStar, we identified the protein cargo of MSC-EVs infused intravenously to rhesus monkeys 24 h and 2 weeks post-injury to the motor cortex. We then analyzed global protein expression changes across cerebrospinal fluid (CSF), plasma, and brain tissue of MSC-EV-treated versus vehicle-treated female, aged rhesus monkeys. A total of 1241/431/4124 monkey proteins were reliably quantified in CSF/plasma/tissue samples, respectively. Longitudinal analysis of CSF and plasma samples highlighted a shift from MSC-EV modulation of inflammatory and metabolic proteins in plasma at early recovery (2 weeks), toward modulation of plasticity-related proteins in CSF and brain tissue at later stages (4 weeks). Further protein-protein interaction analysis identified potential MSC-EV targets related to complementary signaling, proteolysis, and aminoglycan stability, which aligned with our previous findings. This comprehensive, multicompartment monkey proteomics study advances understanding of MSC-EV contents and treatment effects, paving the way for novel treatment of cortical injury.
Medical Subject Headings
Animals; Extracellular Vesicles; Proteomics; Macaca mulatta; Female; Mesenchymal Stem Cells; Disease Models, Animal; Brain Injuries; Proteome; Motor Cortex
PubMed ID
41032466
ePublication
ePub ahead of print
Volume
24
Issue
11
First Page
5664
Last Page
5682
