ADSC-Conditioned Medium Mitigates LPS-Induced Acute Lung Injury by Inhibiting Alveolar Macrophage Pyroptosis

Area of Science:

• Pulmonary Medicine
• Regenerative Medicine
• Cell Biology

Background:

• Acute lung injury (ALI) presents significant mortality due to severe pulmonary inflammation.
• Current pharmacological treatments for ALI are limited.
• Adipose-derived mesenchymal stem cell-conditioned medium (ADSC-CM) offers a potential cell-free therapeutic approach.

Purpose of the Study:

• To investigate the protective effects of ADSC-CM in a rat model of lipopolysaccharide (LPS)-induced ALI.
• To elucidate the underlying mechanisms by which ADSC-CM exerts its therapeutic effects.
• To evaluate ADSC-CM as a cell-free therapeutic platform for ALI management.

Main Methods:

• Established a rat model of LPS-induced ALI.
• Administered ADSC-CM systemically to ALI model rats.
• Analyzed pulmonary pathology, systemic cytokine levels, and pyroptosis markers in lung tissues.
• Conducted in vitro studies using NR8383 alveolar macrophage (AM) cell line to examine signaling pathways.

Main Results:

• ADSC-CM administration significantly reduced lung pathological damage and systemic inflammatory cytokine levels.
• ADSC-CM inhibited pyroptosis in lung tissues.
• In vitro, ADSC-CM suppressed the TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD signaling pathways in AMs, primarily via TLR4 downregulation.

Conclusions:

• ADSC-CM demonstrates significant therapeutic efficacy in mitigating LPS-induced ALI in rats.
• ADSC-CM effectively modulates pyroptosis and inflammatory responses in alveolar macrophages.
• These findings provide a strong mechanistic basis for developing ADSC-CM as a cell-free therapy for ALI.