title: Intrapulmonary delivery of human umbilical cord mesenchymal stem cells attenuates acute lung injury by expanding CD4+CD25+ Forkhead Boxp3 (FOXP3)+ regulatory T cells and balancing anti- and pro-inflammatory factors.
abstract: BACKGROUND
  Systemic and local inflammatory processes play key, mainly detrimental roles in the pathophysiology of acute lung injury (ALI). The present study was designed to determine whether human umbilical cord mesenchymal stem cells (UCMSC) are able to act on CD4(+)CD25(+) Foxp3(+)Treg cells and lead to an improvement in ALI.
  
  
  METHODS
  Mice were administered intratracheally endotoxin (lipopolysaccharide [LPS]) and received intrapulmonary 1×10(6) UCMSC 4 hours after challenge. The CD4(+)CD25(+) Foxp3(+)Treg, survival time, body weight, histology and lung injury scores were assessed after transplantation of UCMSC. In addition, anti-inflammatory factor IL10 and pro-inflammatory mediators production including tumor necrosis factor-a (TNF-α), macrophage inflammatory protein-2(MIP-2) and interferon-γ (IFN-γ) were detected.
  
  
  RESULTS
  Transplantation of UCMSC resulted in significant increase in the level of CD4(+)CD25(+) Foxp3(+)Treg in ALI. Increased level of anti-inflammatory factor IL-10 and reduced levels of TNF-α, MIP-2 and IFN-γ were simultaneously observed in ALI in comparison with control mice.
  
  
  CONCLUSIONS
  Our data demonstrate for the first time that transplantation of UCMSC ameliorates ALI by enhancing the diminished levels of alveolar CD4(+)CD25(+) Foxp3(+)Treg and balancing anti- and pro-inflammatory factors in ALI mice.
authors.affiliation: The State Key Laboratory of Experimental Hematology, National Engineering Technology Research Center of Stem Cells, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences, 288 Nanjing Road, Tianjin, China. sunjun2008387@gmail.com
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
authors.forename: Zhi-Bo
authors.initials: ZB
authors.lastname: Han
authors.forename: Wenbin
authors.initials: W
authors.lastname: Liao
authors.forename: Shao Guang
authors.initials: SG
authors.lastname: Yang
authors.forename: ZhouXin
authors.initials: Z
authors.lastname: Yang
authors.forename: JingXia
authors.initials: J
authors.lastname: Yu
authors.forename: Lei
authors.initials: L
authors.lastname: Meng
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.forename: Zhong Chao
authors.initials: ZC
authors.lastname: Han
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000628:therapy; D000818:Animals; D054426:Chemokine CXCL2 / Q000096:biosynthesis / Q000276:immunology; D036101:Cord Blood Stem Cell Transplantation; D005260:Female; D005333:Fetus; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008070:Lipopolysaccharides / Q000009:adverse effects; D018655:Lymphocyte Count; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D058408:Th1-Th2 Balance; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma