Multiomics reveal human umbilical cord mesenchymal stem cells improving acute lung injury via the lung-gut axis  

作　　者：Lu Lv En-Hai Cui Bin Wang Li-Qin Li Feng Hua Hua-Dong Lu Na Chen Wen-Yan Chen 

机构地区：[1]Department of Respiratory and Critical Care Medicine,Huzhou Central Hospital,Affiliated Huzhou Hospital,Zhejiang University School of Medicine,Huzhou 313000,Zhejiang Province,China [2]Traditional Chinese Medicine Key Laboratory Cultivation Base of Zhejiang Province for the Development and Clinical Transformation of Immunomodulatory Drugs,Huzhou 313000,Zhejiang Province,China

出　　处：《World Journal of Stem Cells》2023年第9期908-930,共23页世界干细胞杂志（英文版）（电子版）

基　　金：the Key Research and Development Project of Science and Technology Department of Zhejiang Province,No.2019C03041.

摘　　要：BACKGROUND Acute lung injury(ALI)and its final severe stage,acute respiratory distress syndrome,are associated with high morbidity and mortality rates in patients due to the lack of effective specific treatments.Gut microbiota homeostasis,including that in ALI,is important for human health.Evidence suggests that the gut microbiota improves lung injury through the lung-gut axis.Human umbilical cord mesenchymal cells(HUC-MSCs)have attractive prospects for ALI treatment.This study hypothesized that HUC-MSCs improve ALI via the lung-gut microflora.AIM To explore the effects of HUC-MSCs on lipopolysaccharide(LPS)-induced ALI in mice and the involvement of the lung-gut axis in this process.METHODS C57BL/6 mice were randomly divided into four groups(18 rats per group):Sham,sham+HUC-MSCs,LPS,and LPS+HUC-MSCs.ALI was induced in mice by intraperitoneal injections of LPS(10 mg/kg).After 6 h,mice were intervened with 0.5 mL phosphate buffered saline(PBS)containing 1×10^(6) HUC-MSCs by intraperitoneal injections.For the negative control,100 mL 0.9%NaCl and 0.5 mL PBS were used.Bronchoalveolar lavage fluid(BALF)was obtained from anesthetized mice,and their blood,lungs,ileum,and feces were obtained by an aseptic technique following CO_(2) euthanasia.Wright’s staining,enzyme-linked immunosorbent assay,hematoxylin-eosin staining,Evans blue dye leakage assay,immunohistochemistry,fluorescence in situ hybridization,western blot,16S rDNA sequencing,and non-targeted metabolomics were used to observe the effect of HUC-MSCs on ALI mice,and the involvement of the lung-gut axis in this process was explored.One-way analysis of variance with post-hoc Tukey’s test,independent-sample Student’s t-test,Wilcoxon rank-sum test,and Pearson correlation analysis were used for statistical analyses.RESULTS HUC-MSCs were observed to improve pulmonary edema and lung and ileal injury,and decrease mononuclear cell and neutrophil counts,protein concentrations in BALF and inflammatory cytokine levels in the serum,lung,and ileum of ALI mice.Especially

关 键 词：Acute lung injury Human umbilical cord mesenchymal cells LIPOPOLYSACCHARIDE MICROFLORA Untargeted metabolomics Toll-like receptor 4/nuclear factor kappa-B signaling pathway 

分 类 号：R745[医药卫生—神经病学与精神病学]