DOI: https://doi.org/10.21203/rs.3.rs-440197/v1
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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