OBJECTIVE To explore the therapeutic effects of apoptotic vesicles (ApoVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) on lipopolysaccharide (LPS)-induced injury in mouse alveolar macrophages (MH-S) and acute lung injury (ALI).

METHODS In cell experiments, MH-S cells were induced to injury with 100 ng/ml LPS and treated with different concentrations of ApoVs (10⁴~10⁸ particles/ml) for 24 hours. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of inflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α). In animal experiments, a mouse ALI model was established by intratracheal injection of 5 mg/kg LPS. Two hours later, different doses of ApoVs (10, 20, 40 μg/mouse) were injected intravenously through the tail vein. Samples were collected after 24 hours, and the pathological changes in lung tissues were observed through hematoxylin-eosin staining. RT-qPCR was used to detect inflammatory cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lung tissues. Enzyme-linked immunosorbent assay (ELISA) was employed to detect the levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and serum.

RESULTS Cell experiments showed that ApoVs at concentrations of 10⁶and 10⁷ particles/ml reduced the expression of IL-1β, IL-6 and TNF-α in MH-S cells (P < 0.05), while no significant improvement was observed in the 10⁸ particles/ml group. Animal experiments revealed that the pathological scores of lung tissues in the group treated with ApoVs at doses of 10 μg/mouse and 20 μg/mouse significantly reduced (P < 0.05), as well as the expression of IL-1β, IL-6, TNF-α, iNOS and COX-2 in lung tissue, BALF and serum (P < 0.05), whereas no significant improvement was observed in the 40 μg/mouse group.

CONCLUSIONS ApoVs derived from hUCMSCs can effectively alleviate LPS-induced infectious ALI at both the cellular and animal levels. The therapeutic effect does not increase with increasing dose, indicating the existence of an optimal concentration window.