Allogeneic human umbilical cord-derived mesenchymal stem cells reduce lipopolysaccharide-induced inflammation and acute lung injury

Acute lung injury (ALI) is the clinical disorder of acute hypoxemic respiratory deficiency and it is associated with a high mortality rate. Increased lung permeability, infiltration of inflammatory cells, secretion of inflammatory cytokines, and pulmonary edema are hallmarks of ALI. Currently, there is no effective pharmacological agent approved for ALI, and the treatment regimens available are mostly supportive. Mesenchymal stem cells (MSCs) are multipotent stromal cells with immunomodulating potential, which therefore hold great promise for the treatment of ALI. We established an LPS-induced ALI mouse model by intratracheal injection of lipopolysaccharide (LPS). Human umbilical cord-derived MSCs (hUC-MSCs) were delivered through the tail vein to assess the effects of MSCs on relieving LPS-induced ALI. Intratracheal injection of LPS increased the infiltration of neutrophils and enhanced the expression of pro-inflammatory cytokines, such as IL-6, IL-1β and TNF-α. Administration of hUC-MSCs decreased pathological signs of inflammation, as well as reduced ALI scores. The levels of IL-6, IL-1β and TNF-α were also dose-dependently inhibited in the bronchoalveolar lavage fluids from damaged lung tissues. Moreover, MPO and BAX levels were decreased by the hUC-MSC treatment, suggesting hUC-MSCs may play the role in inhibiting ROS production and apoptotic death in ALI repair. These results highlight the potential of hUC-MSCs to alleviate bacterial endotoxin-induced inflammation, and may represent an effective modality for the treatment of ALI in clinical settings.