title: Intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells attenuates Escherichia coli-induced acute lung injury in mice.
abstract: BACKGROUND
  Human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) attenuate hyperoxic neonatal lung injury primarily through anti-inflammatory effects. We hypothesized that intratracheal transplantation of human UCB-derived MSCs could attenuate Escherichia coli (E. coli)-induced acute lung injury (ALI) in mice by suppressing the inflammatory response.
  
  
  METHODS
  Eight-week-old male ICR mice were randomized to control or ALI groups. ALI was induced by intratracheal E. coli instillation. Three-hours after E. coli instillation, MSCs, fibroblasts or phosphate-buffered saline were intratracheally administered randomly and survival was analyzed for 7 days post-injury. Lung histology including injury scores, myeloperoxidase (MPO) activity, and protein levels of interleukin (IL)-1α, IL-1β, IL-6, tumor necrosis factor (TNF)-α, and macrophage inflammatory protein (MIP)-2 as well as the wet-dry lung ratio and bacterial counts from blood and bronchoalveolar lavage (BAL) were evaluated at 1, 3, and 7 days post-injury. Levels of inflammatory cytokines in the lung were also profiled using protein macroarrays at day 3 post-injury which showed peak inflammation.
  
  
  RESULTS
  MSC transplantation increased survival and attenuated lung injuries in ALI mice, as evidenced by decreased injury scores on day 3 post-injury and reduced lung inflammation including increased MPO activity and protein levels of IL-1α, IL-1β, IL-6, TNF-α, and MIP-2 on day 3 and 7 post-injury. Inflammatory cytokine profiles in the lungs at day 3 post-injury were attenuated by MSC transplantation. MSCs also reduced the elevated lung water content at day 3 post-injury and bacterial counts in blood and BAL on day 7 post-injury.
  
  
  CONCLUSIONS
  Intratracheal transplantation of UCB-derived MSCs attenuates E. coli-induced ALI primarily by down-modulating the inflammatory process and enhancing bacterial clearance.
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Kim
authors.forename: Yun Sil
authors.initials: YS
authors.lastname: Chang
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Choi
authors.forename: Jin Kyu
authors.initials: JK
authors.lastname: Kim
authors.forename: Hey Soo
authors.initials: HS
authors.lastname: Yoo
authors.forename: So Yoon
authors.initials: SY
authors.lastname: Ahn
authors.forename: Dong Kyung
authors.initials: DK
authors.lastname: Sung
authors.forename: Soo Yoon
authors.initials: SY
authors.lastname: Kim
authors.forename: Ye Rim
authors.initials: YR
authors.lastname: Park
authors.forename: Won Soon
authors.initials: WS
authors.lastname: Park
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D054426:Chemokine CXCL2 / Q000378:metabolism; D036101:Cord Blood Stem Cell Transplantation; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000472:pathogenicity*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053582:Interleukin-1alpha / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000601:surgery*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009195:Peroxidase / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000601:surgery*; D040081:Protein Array Analysis; D011654:Pulmonary Edema / Q000382:microbiology / Q000517:prevention & control; D012720:Severity of Illness Index; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase