Extracellular vesicle-mediated cell-cell communication in keloids and hypertrophic scars: mechanisms, methodological caveats, and therapeutic perspectives

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Pathological scarring, including keloids and hypertrophic scars, remains a major clinical challenge characterized by persistent fibroblast activation, excessive extracellular matrix deposition, chronic inflammation, and aberrant tissue remodeling. Although current treatments have improved management, high recurrence rates and variable outcomes indicate that the underlying mechanisms remain incompletely understood. Extracellular vesicles (EVs), especially small extracellular vesicles (sEVs), are increasingly recognized as mediators of intercellular communication in fibrotic skin disorders. However, according to MISEV recommendations, the term "exosome" should be used cautiously unless endosomal origin is specifically demonstrated. In pathological scars, EV-/sEV-mediated signaling has been implicated in fibroblast activation, immune dysregulation, angiogenic imbalance, and extracellular matrix remodeling through cargo transfer among fibroblasts, keratinocytes, endothelial cells, immune cells, and mesenchymal stromal/stem cells. Reported downstream pathways include TGF-β/Smad, Wnt/β-catenin, PI3K/Akt, and NF-κB. However, the strength of evidence varies substantially, as many conclusions are based on in vitro studies or correlative omics analyses rather than direct causal experiments. In addition, differences in EV isolation and characterization methods may significantly affect rep

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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