title: Murine model: maternal administration of stem cells for prevention of prematurity.
abstract: OBJECTIVE
  Using a mouse model of intrauterine inflammation, we have demonstrated that exposure to inflammation induces preterm birth and perinatal brain injury. Mesenchymal stem cells (MSCs) have been shown to exhibit immunomodulatory effects in many inflammatory conditions. We hypothesized that treatment with human adipose tissue-derived MSCs may decrease the rate of preterm birth and perinatal brain injury through changes in antiinflammatory and regulatory milieu.
  
  
  METHODS
  A mouse model of intrauterine inflammation was used with the following groups: (1) control; (2) intrauterine inflammation (lipopolysaccharide); and (3) intrauterine lipopolysaccharide+intraperitoneal (MSCs). Preterm birth was investigated. Luminex multiplex enzyme-linked immunosorbent assays were performed for protein levels of cytokines in maternal and fetal compartments. Immunofluorescent staining was used to identify and localize MSCs and to examine microglial morphologic condition and neurotoxicity in perinatal brain. Behavioral testing was performed at postnatal day 5.
  
  
  RESULTS
  Pretreatment with MSCs significantly decreased the rate of preterm birth by 21% compared with the lipopolysaccharide group (P<.01). Pretreatment was associated with increased interleukin-10 in maternal serum, increased interleukin-4 in placenta, decreased interleukin-6 in fetal brain (P<.05), decreased microglial activation (P<.05), and decreased fetal neurotoxicity (P<.05). These findings were associated with improved neurobehavioral testing at postnatal day 5 (P<.05). Injected MSCs were localized to placenta.
  
  
  CONCLUSIONS
  Maternally administered MSCs appear to modulate maternal and fetal immune response to intrauterine inflammation in the model and decrease preterm birth, perinatal brain injury, and motor deficits in offspring mice.
authors.affiliation: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Jun
authors.initials: J
authors.lastname: Lei
authors.affiliation: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Wance
authors.initials: W
authors.lastname: Firdaus
authors.affiliation: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Rosenzweig
authors.affiliation: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Shorouq
authors.initials: S
authors.lastname: Alrebh
authors.affiliation: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Bakhshwin
authors.affiliation: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Talaibek
authors.initials: T
authors.lastname: Borbiev
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD; The Kennedy Krieger Institute, Baltimore, MD.
authors.forename: Ali
authors.initials: A
authors.lastname: Fatemi
authors.affiliation: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Karin
authors.initials: K
authors.lastname: Blakemore
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD; The Kennedy Krieger Institute, Baltimore, MD.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Johnston
authors.affiliation: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD; The Kennedy Krieger Institute, Baltimore, MD. Electronic address: iburd@jhmi.edu.
authors.forename: Irina
authors.initials: I
authors.lastname: Burd
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D016207:Cytokines / Q000276:immunology*; D003712:Dendrites / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004716:Endometritis / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D011247:Pregnancy; D047928:Premature Birth / Q000276:immunology / Q000517:prevention & control*
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016753:Interleukin-10
keywords: intrauterine inflammation; mesenchymal stem cell; perinatal brain injury; preterm birth