To investigate the effects of extracellular vesicles derived from induced pluripotent stem cell-derived mesenchymal stem cells (iMSC-EVs) on immune dysfunction in patients with surgical sepsis.
Approach:
Patient Enrollment: Fifty-three patients with surgical sepsis meeting Sepsis-3 criteria were prospectively enrolled.
Mortality Assessment: Sixty-day mortality was used to define survivor (n=26) and non-survivor (n=27) groups.
Statistical Analysis: Logistic regression identified mediators independently associated with mortality and SOFA score.
Cytokine Profiling: Cytokine profiles in plasma and media were quantified by ELISA.
PBMC Treatment: Peripheral blood mononuclear cells (PBMCs) were isolated and treated with LPS, iMSC-EVs, or both.
Assessment of Apoptosis: Apoptosis, caspase-3 expression, and acute-phase markers (CRP, SAA) were assessed.
Key Findings:
Increased age, cancer diagnosis, and SOFA score were associated with mortality.
Non-survivors exhibited significantly elevated IL-10, MCP-1, and IL-10/TNF-α ratio, with a lower IL-6/IL-10 ratio.
IL-10, MCP-1, and IL-10/TNF-α ratio independently predicted 60-day mortality.
LPS-stimulated PBMCs from non-survivors showed a distinct pattern of cytokine responses compared to survivors.
iMSC-EV treatment attenuated LPS-induced inflammation and reduced apoptosis and caspase-3 activation.
Interpretation:
Patient characteristics and cytokine levels were associated with 60-day sepsis mortality and reflect immunosuppression severity. iMSC-EVs exert immunomodulatory and cytoprotective effects on septic patient-derived PBMCs.
Limitations:
The study is limited by the small sample size.
Findings may not be generalizable beyond the studied population.
Conclusion:
iMSC-EVs may have potential as a therapeutic strategy for restoring immune homeostasis in sepsis.
