title: HB-EGF augments the ability of mesenchymal stem cells to attenuate intestinal injury.
abstract: BACKGROUND
  We have previously demonstrated that heparin-binding EGF-like growth factor (HB-EGF) and mesenchymal stem cell (MSC) administration protect the intestines from ischemia/reperfusion (I/R) injury in vivo, with amniotic fluid-derived MSC (AF-MSC) being more efficacious than bone marrow-derived MSC (BM-MSC). The goal of the current study was to determine whether the protective effects of HB-EGF were from direct effects on MSC or via alternative mechanisms.
  
  
  METHODS
  Murine MSC were transfected with an HB-EGF plasmid or control plasmid by electroporation. Mice were subjected to segmental intestinal I/R injury and received either BM-MSC or AF-MSC either with or without exogenous HB-EGF, or BM-MSC or AF-MSC that endogenously over-expressed HB-EGF. MSC engraftment, intestinal histologic injury, and intestinal permeability were quantified.
  
  
  RESULTS
  There was increased MSC engraftment into injured compared to uninjured intestine. HB-EGF increased AF-MSC engraftment into injured intestine. Administration of HB-EGF and MSC improved intestinal histology and intestinal permeability after I/R injury, with AF-MSC being most efficacious. The effect of HB-EGF on MSC was similar when the growth factor was administered exogenously, or when it was overexpressed endogenously.
  
  
  CONCLUSIONS
  The effect of HB-EGF on AF-MSC was similar with both exogenous administration and endogenous overexpression of the growth factor, implying that HB-EGF has a direct effect on AF-MSC. This information may assist in guiding potential future AF-MSC-based therapies for patients at risk of intestinal ischemic injuries.
authors.affiliation: The Research Institute at Nationwide Children's Hospital, Center for Perinatal Research, Department of Pediatric Surgery, Nationwide Children's Hospital, and The Ohio State University College of Medicine, Columbus, Ohio.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Watkins
authors.affiliation: The Research Institute at Nationwide Children's Hospital, Center for Perinatal Research, Department of Pediatric Surgery, Nationwide Children's Hospital, and The Ohio State University College of Medicine, Columbus, Ohio.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: The Research Institute at Nationwide Children's Hospital, Center for Perinatal Research, Department of Pediatric Surgery, Nationwide Children's Hospital, and The Ohio State University College of Medicine, Columbus, Ohio.
authors.forename: Mika A B
authors.initials: MA
authors.lastname: Matthews
authors.affiliation: The Research Institute at Nationwide Children's Hospital, Center for Perinatal Research, Department of Pediatric Surgery, Nationwide Children's Hospital, and The Ohio State University College of Medicine, Columbus, Ohio.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: The Research Institute at Nationwide Children's Hospital, Center for Perinatal Research, Department of Pediatric Surgery, Nationwide Children's Hospital, and The Ohio State University College of Medicine, Columbus, Ohio. Electronic address: gail.besner@nationwidechildrens.org.
authors.forename: Gail E
authors.initials: GE
authors.lastname: Besner
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D066257:Heparin-binding EGF-like Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D007422:Intestines / Q000098:blood supply*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011270:Pregnancy, Animal; D012333:RNA, Messenger / Q000235:genetics; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D066257:Heparin-binding EGF-like Growth Factor; D012333:RNA, Messenger
keywords: Amniotic fluid; Bone marrow; Heparin-binding EGF-like growth factor; Intestinal injury; Ischemia/reperfusion; Mesenchymal stem cells