Apoptotic Vesicles Attenuate Acute Lung Injury
Summary
In an LPS-induced murine ALI model, mesenchymal stem cell–derived apoptotic vesicles administered 2 hours after injury reduced platelet activation, neutrophil infiltration, and NETosis, ameliorating lung injury. ApoVs were enriched in CD73, and CD73 was essential for suppressing platelet activation/NETosis and for the therapeutic effect.
Key Findings
- In LPS-induced murine ALI, apoVs administered 2 hours post-injury reduced platelet activation, neutrophil infiltration, and NETosis, alleviating lung injury.
- ApoVs were enriched with CD73, which was necessary for suppressing platelet activation and neutrophil NETosis.
- CD73 was critical for the observed therapeutic effects of apoVs in lung injury.
Clinical Implications
While preclinical, the findings nominate CD73 and the platelet–NET axis as therapeutic targets and support development of apoV-based biologics for ARDS. They also suggest exploring adjunctive strategies that augment adenosine signaling to dampen thromboinflammation.
Why It Matters
This work identifies a CD73-dependent, cell-free therapeutic approach that targets the platelet–neutrophil axis, a key driver of ALI/ARDS pathobiology. It provides mechanistic insight and a translationally attractive modality beyond whole-cell therapies.
Limitations
- Single preclinical model (LPS ALI) without validation in additional models or species
- No human data; dose, safety, and manufacturing parameters are undefined
Future Directions
Validate apoV efficacy across diverse ALI/ARDS models and large animals, define dosing/safety and GMP manufacturing, and test CD73/adenosine-pathway augmentation as adjuncts. Early-phase clinical translation with pharmacodynamic biomarkers is warranted.
Study Information
- Study Type
- Case-control
- Research Domain
- Pathophysiology
- Evidence Level
- V - Preclinical mechanistic study in an animal ALI model
- Study Design
- OTHER