Comparison of efficacy of exosomes derived from human umbilical cord blood mesenchymal stem cells in treating mouse acute lung injury via different routes.

OBJECTIVE

To investigate the therapeutic efficacy of human umbilical cord blood mesenchymal stem cell-derived exosomes (hUCMSC-Exo) in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model and compare the effects of different administration routes.

METHODS

An ALI mouse model was established through intratracheal LPS injection. Mice received hUCMSC-Exo through tail vein injection, nasal drip, or atomization at 4-and-24 h post-modeling, with comparisons made across low, medium, and high doses. Mice were categorized into three groups: control, LPS model, and experimental ( = 8). Histopathological scoring assessed lung inflammation after 48 h; and inflammatory cytokine levels (TNF-α, IL-6, IL-1β, and IL-10) in serum and bronchoalveolar lavage fluid (BALF) were quantified by enzyme-linked immunosorbent assay (ELISA).

RESULTS

In a murine model of LPS-induced ALI, administration of hUCMSC-Exo via intravenous, intranasal, or nebulized routes at 4 and 24 h post-LPS exposure significantly attenuated pulmonary inflammation, as evidenced by reduced alveolar inflammatory cell infiltration, hemorrhage, and edema in histopathological analysis (except the nebulized low-dose group). ELISA revealed that hUCMSC-Exo markedly decreased serum and bronchoalveolar lavage fluid (BALF) levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β ( < 0.05) while increasing IL-10 levels. Dose-dependent effects were observed across routes: intravenous high-dose (Exo-VH) outperformed medium- and low-dose groups ( < 0.05); intranasal medium-dose (Exo-NM) was superior to low-dose (Exo-NL;  < 0.05), with no significant difference between medium and high doses ( > 0.05); nebulized high-dose (Exo-AH) demonstrated enhanced efficacy over medium- (Exo-AM;  < 0.05) and low-dose (Exo-AL;  < 0.05). At an equivalent dose (5 × 10⁸ particles), intravenous delivery achieved superior lung injury score reduction and cytokine modulation compared to intranasal and nebulized routes ( < 0.05), whereas the latter two showed comparable efficacy ( > 0.05). These findings collectively highlight the therapeutic potential of hUCMSC-Exo in ALI, with intravenous administration emerging as the optimal route at the tested dose.

CONCLUSION

hUCMSC-Exo effectively attenuates LPS-induced ALI in mice. At the tested dose (5 × 10⁸ particles), intravenous delivery exhibited superior therapeutic efficacy over intranasal and nebulized routes.