Authors: Salinas-Varas Constanza, Espinosa Gabriel, Muñoz-Caro Tamara, Conejeros Iván, Gärtner Ulrich, Fey Kerstin, Arnhold Stefan, Taubert Anja, Hermosilla Carlos
Journal: Frontiers in veterinary science
Summary
# Editorial Summary Neutrophil extracellular traps (NETs) are web-like DNA structures released by activated neutrophils during infection and inflammation, but excessive NET formation can drive tissue damage and perpetuate chronic inflammatory conditions in equine patients. Salinas-Varas and colleagues investigated whether adipose-derived stem cells (ADSCs)—increasingly used in regenerative medicine for their anti-inflammatory properties—could modulate NET formation by equine neutrophils in vitro, isolating ADSCs from both subcutaneous and retroperitoneal fat stores and co-culturing them with blood neutrophils stimulated to produce NETs via phorbol 12-myristate 13-acetate (PMA) and ionomycin. Using scanning electron and immunofluorescence microscopy alongside extracellular DNA quantification, the researchers demonstrated that ADSCs significantly suppressed NET release in a dose-dependent manner, with greater ADSC-to-neutrophil ratios producing more pronounced inhibition, despite having no measurable effect on reactive oxygen species production. These findings suggest that ADSCs exert their immunomodulatory effects through mechanisms independent of oxidative burst suppression, opening new perspectives for treating conditions characterised by excessive neutrophil activation—such as acute respiratory distress, sepsis, and certain musculoskeletal inflammatory states in horses. Further investigation into the specific molecular pathways governing this NET-inhibitory capacity will be essential before translating these observations into clinical applications, particularly regarding optimal cell ratios, timing of administration, and efficacy in vivo.
Read the full abstract on PubMed
Practical Takeaways
- •ADSC therapy may help regulate excessive innate immune responses in equine inflammatory conditions by reducing NET-mediated tissue damage, though translation to clinical use requires further investigation
- •The dose-dependent nature of ADSC effects on NET formation suggests optimization of cell-to-target ratios may be important for therapeutic efficacy in regenerative medicine applications
- •ADSC immunomodulation appears to work through mechanisms independent of ROS suppression, indicating multiple potential pathways for therapeutic effect in treating inflammatory conditions
Key Findings
- •Equine adipose-derived stem cells (ADSCs) significantly reduced NET formation by equine polymorphonuclear neutrophils (PMN) when co-cultured with PMA stimulation
- •NET inhibition by ADSCs was dose-dependent, with effectiveness correlating to ADSC-to-PMN ratio in both PMA and ionomycin-stimulated PMN
- •ADSCs did not modulate reactive oxygen species (ROS) production by equine PMN despite their anti-NET effects
- •ADSCs from both subcutaneous and retroperitoneal adipose sources demonstrated comparable immunomodulatory effects on NET formation