title: Administration of bone marrow stromal cells in sepsis attenuates sepsis-related coagulopathy.
abstract: BACKGROUND
  Coagulopathy plays an important role in sepsis. The aim of this study was to determine whether bone marrow stromal cell (BMSC) administration could attenuate coagulopathy in sepsis.
  
  
  METHODS
  In vitro: endothelial cells were cultured with/without BMSCs for 6 h following LPS stimulation and were collected for thrombomodulin (TM) and endothelial protein C receptor (EPCR) measurements. In vivo: Thirty-six mice were randomized into sham, sepsis, and sepsis + BMSC groups (n = 12 each group). Sepsis was induced through cecal ligation and puncture (CLP). BMSC infusion was started at 6 h after CLP. Lung tissues and plasma samples were collected at 24 h after CLP for enzyme-linked immunosorbent assay (ELISA), quantitative real-time RT-PCR, western blot, and immunohistochemistry analysis.
  
  
  RESULTS
  In vitro: BMSCs attenuated the decrease in TM and EPCR mRNA and protein expression levels in LPS-stimulated endothelial cells. In vivo: BMSC treatment decreased lung injury and mesenteric perfusion impairment, and ameliorated coagulopathy, as suggested by the reduction in elevated TF, vWF, and TAT circulation levels. BMSC infusion decreased TF mRNA transcription and protein expression levels in lung tissues, and increased TM and EPCR mRNA transcription and expression levels.
  
  
  CONCLUSIONS
  BMSC administration attenuated coagulopathy, and decreased lung injury and mesenteric perfusion impairment in sepsis. Key messages BMSCs increased the expression of TM and EPCR from endothelium cells exposed to LPS in vitro. BMSC treatment attenuated lung injury and coagulopathy in the mice cecal ligation and puncture (CLP) model. BMSC administration-attenuated coagulopathy is related to the reduced expression of TF and increased expression of TM and EPCR.
authors.affiliation: a Department of the First Clinical Medical , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , Zhejiang , People's Republic of China ;
authors.forename: Lifei
authors.initials: L
authors.lastname: Tan
authors.affiliation: b Department of Intensive Care Unit , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , Zhejiang , People's Republic of China ;
authors.forename: Yueyue
authors.initials: Y
authors.lastname: Huang
authors.affiliation: a Department of the First Clinical Medical , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , Zhejiang , People's Republic of China ;
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Pan
authors.affiliation: c Department of General Medicine , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , Zhejiang , People's Republic of China ;
authors.forename: Shichao
authors.initials: S
authors.lastname: Quan
authors.affiliation: a Department of the First Clinical Medical , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , Zhejiang , People's Republic of China ;
authors.forename: Shunyao
authors.initials: S
authors.lastname: Xu
authors.affiliation: d Department of Traumatology , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , Zhejiang , People's Republic of China.
authors.forename: Dequan
authors.initials: D
authors.lastname: Li
authors.affiliation: a Department of the First Clinical Medical , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , Zhejiang , People's Republic of China ;
authors.forename: Lijun
authors.initials: L
authors.lastname: Song
authors.affiliation: a Department of the First Clinical Medical , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , Zhejiang , People's Republic of China ;
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: b Department of Intensive Care Unit , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , Zhejiang , People's Republic of China ;
authors.forename: Wanzhou
authors.initials: W
authors.lastname: Chen
authors.affiliation: b Department of Intensive Care Unit , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , Zhejiang , People's Republic of China ;
authors.forename: Jingye
authors.initials: J
authors.lastname: Pan
mesh_terms: D000818:Animals; D001778:Blood Coagulation Disorders / Q000209:etiology / Q000517:prevention & control*; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D000074283:Endothelial Protein C Receptor; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D055370:Lung Injury / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics; D018805:Sepsis / Q000150:complications*; D018180:Thrombomodulin / Q000235:genetics
chemical_list: D000074283:Endothelial Protein C Receptor; C080248:Procr protein, mouse; D011956:Receptors, Cell Surface; D018180:Thrombomodulin
keywords: BMSC; cecal ligation and puncture; endothelial cells; mice; sepsis and coagulopathy