title: Human CD34+ progenitor cells freshly isolated from umbilical cord blood attenuate inflammatory lung injury following LPS challenge.
abstract: Adult stem cell-based therapy is a promising novel approach for treatment of acute lung injury. Here we investigated the therapeutic potential of freshly isolated human umbilical cord blood CD34(+) progenitor cells (fCB-CD34(+) cells) in a mouse model of acute lung injury. At 3 h post-lipopolysaccharide (LPS) challenge, fCB-CD34(+) cells were transplanted i.v. to mice while CD34(-) cells or PBS were administered as controls in separate cohorts of mice. We observed that fCB-CD34(+) cell treatment inhibited lung vascular injury evident by decreased lung vascular permeability. In contrast, CD34(-) cells had no effects on lung vascular injury. Lung inflammation determined by myeloperoxidase activity, neutrophil sequestration and expression of pro-inflammatory mediators was attenuated in fCB-CD34(+) cell-treated mice at 26 h post-LPS challenge compared to PBS or CD34(-) cell-treated controls. Importantly, lung inflammation in fCB-CD34(+) cell-treated mice was returned to normal levels as seen in basal mice at 52 h post-LPS challenge whereas PBS or CD34(-) cell-treated control mice exhibited persistent lung inflammation. Accordingly, fCB-CD34(+) cell-treated mice exhibited a marked increase of survival rate. Employing in vivo 5-bromo-2'-deoxyuridine incorporation assay, we found a drastic induction of lung endothelial proliferation in fCB-CD34(+) cell-treated mice at 52 h post-LPS compared to PBS or CD34(-) cell-treated controls, which contributed to restoration of vascular integrity and thereby inhibition of lung inflammation. Taken together, these data have demonstrated the protective effects of fCB-CD34(+) cell on acute lung injury induced by LPS challenge, suggesting fCB-CD34(+) cells are an important source of stem cells for the treatment of acute lung injury.
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois, United States of America ; Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, United States of America ; Department of Pharmacology, School of Medical Sciences and Laboratory Medicine, Jiangsu University, Zhenjiang, China.
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois, United States of America ; Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois, United States of America ; Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.
authors.forename: Yidan D
authors.initials: YD
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois, United States of America ; Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Vogel
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Yuanling
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Medicine, University of Illinois College of Medicine, Chicago, Illinois, United States of America.
authors.forename: Nadim
authors.initials: N
authors.lastname: Mahmud
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois, United States of America ; Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.
authors.forename: You-Yang
authors.initials: YY
authors.lastname: Zhao
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D049109:Cell Proliferation; D002469:Cell Separation; D042783:Endothelial Cells / Q000166:cytology; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000628:therapy; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D016019:Survival Analysis
chemical_list: D018952:Antigens, CD34; D008070:Lipopolysaccharides