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Mesenchymal stem cells (MSCs) are associated with pulmonary protection and longevity. We separated chicken bone marrow-derived mesenchymal stem cells (BM-MSCs); investigated whether BM-MSCs can improve lipopolysaccharide (LPS)-induced lung and distal organ injury; and explored the underlying mechanisms. Ninety-six male ICR (6 weeks old) mice were randomly divided into three groups: Sham, LPS, and LPS + MSC groups. The mice were intratracheally injected with 5 mg/kg LPS to induce acute lung injury (ALI). The histopathological severity of injury to the lung, liver, kidney, heart, and aortic tissues was detected. Wet/dry ratio, protein concentrations in bronchoalveolar lavage fluid (BALF), BALF cell counts, inflammatory cytokine levels in serum, inflammatory cytokine gene expression, and oxidative stress-related indicators were detected. In addition, a survival analysis was performed in sixty male ICR mice (6 weeks old, 18–20 g). This study used chicken BM-MSCs, which are easier to obtain and more convenient than other animal or human MSCs, and have MSC-associated properties, such as a colony forming ability, multilineage differentiation potential, and certain phenotypes. BM-MSCs administration significantly improved the survival rate, systemic inflammation, and the histopathological severity of lung, liver, kidney, and aortic injury during ALI. BM-MSCs administration reduced the levels of inflammatory factors in BALF, the infiltration of neutrophils, and oxidative stress injury in lung tissue. In addition, BM-MSCs administration reduced TRL4 and Mdy88 mRNA expression during ALI. Chicken BM-MSCs serve as a potential alternative resource for stem cell therapy and exert a prominent effect on LPS-induced ALI and extrapulmonary injury, in part through TRL4/Mdy88 signaling and inhibition of neutrophil inflammation and oxidative stress injury.

Objective: Mesenchymal stem cells (MSCs) were an emergent tool to prevent acute lung injury (ALI) and its complications. We attempted to isolate, culture, and characterize chicken bone marrow-derived mesenchymal stem cells (BM-MSCs), investigate whether BM-MSCs protect against lipopolysaccharide (LPS)-induced ALI, and explore the related mechanisms. Methods: Ninety-six male ICR (6 wks old) mice were divided into three groups: Con, LPS, and LPS + MSC. Mice in the LPS and Ex+LPS groups received 5 mg/kg LPS intratracheally to induce ALI. Histopathological micrographs showed morphological changes in the lung, heart, liver, kidney, and aorta. Lung permeability, bronchoalveolar lavage fluid (BALF) cell counts, oxidative stress parameters, and inflammatory cytokine levels in the BALF, plasma, and lung tissue were detected. Furthermore, gene expression levels for Toll-Like Receptor 4 (TRL4) and myeloid differentiation factor (Mdy88) were measured. Besides, a survival analysis was performed in sixty male ICR mice. Results: BM-MSCs administration significantly increased the survival rate and decreased the histopathological severity of LPS-induced lung, liver, kidney, and aortic injury. BM-MSC administration improved LPS-induced pulmonary inflammation, systemic inflammation, and oxidative stress injury. BM-MSC administration reduced the infiltration of neutrophils in lung, liver, kidney, and heart tissues. In addition, BM-MSC administration reduced TRL4 and Mdy88 mRNA expression in mice with ALI. Conclusions: Chicken BM-MSCs improved LPS-induced ALI and liver, kidney, heart, and aortic injury. Chicken BM-MSCs improved LPS-induced ALI, in part through TLR4/Myd88 signaling and inhibition of inflammation and oxidative stress injury. BM-MSCs improved LPS-induced pulmonary fibrosis via suppressing TGF-β and MMP-9. BM-MSCs reduced neutrophil content via suppressing CXCL-1, IL-8, and TNF-α.

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