title: Mesenchymal stem cell-based developmental endothelial locus-1 gene therapy for acute lung injury induced by lipopolysaccharide in mice.
abstract: Studies have suggested that bone marrow-derived mesenchymal stem cells (MSCs) may be used as a tool for gene therapy. Developmental endothelial locus-1 (Del-1) is a critical factor for cell migration and infiltration via the inhibition of the function of a major leukocyte adhesion receptor LFA-1 which prevents leukocyte adhesion to the endothelium. In the present study, we hypothesized that MSC-based Del-1 gene therapy may have potential therapeutic applications for lipopolysaccharide (LPS)-induced lung injury. The MSCs in the present assay were isolated from 6 week-old male mice. In order to investigate the therapeutic effect of the Del-1 gene on LPS-induced ALI mice, a lentivirus vector containing the Del-1 gene was constructed and transduced into the MSCs. In the in vivo assay, we induced lung injury with LPS injection and treated mice with different groups of MSCs, and compared with groups treated with MSCs alone, we observed that the administration with MSCs carrying Del-1 (MSCs-Del1) markedly alleviated the LPS-induced lung injury. There were significant decreases in the number of neutrophils in bronchoalveolar lavage (BAL) and the serum levels of TNF-α and IL-6 in the Del-1-expressed MSC-treated mice. Furthermore, compared with MSCs treated alone, Del1-MSC-treated mice also exhibited low lung injury scores, high protein concentrations and myeloperoxidase activity. In conclusion, treatment with Del-1-expressed MSCs significantly decreases the severity of endotoxin-induced acute lung injury and the level of inflammatory cytokines in mice.
authors.affiliation: Department of Respiratory Medicine, Pudong New Area, Gongli Hospital, Shanghai 200135, P.R. China.
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, Pudong New Area, Gongli Hospital, Shanghai 200135, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Institute of Respiratory Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Xue-Ling
authors.initials: XL
authors.lastname: Wu
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000235:genetics* / Q000628:therapy*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D015815:Cell Adhesion Molecules; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D009195:Peroxidase / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C491706:Edil3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase