title: Synergistic effects of HB-EGF and mesenchymal stem cells in a murine model of intestinal ischemia/reperfusion injury.
abstract: BACKGROUND
  We have previously demonstrated that heparin-binding EGF-like growth factor (HB-EGF) administration protects the intestines from ischemia/reperfusion (I/R) injury in vivo. We have also shown that HB-EGF promotes mesenchymal stem cell (MSC) proliferation and migration in vitro. The goals of the current study were to examine the effects of HB-EGF and both bone marrow (BM)- and amniotic fluid (AF)-derived MSC on intestinal I/R injury in vivo.
  
  
  METHODS
  MSC were isolated from pan-EGFP mice, expanded, and purified. Pluripotency was confirmed by induced differentiation. Mice were subjected to terminal ileum I/R and received either: (1) no therapy; (2) HB-EGF; (3) BM-MSC; (4) HB-EGF+BM-MSC; (5) AF-MSC; or (6) HB-EGF+AF-MSC. MSC engraftment, histologic injury, and intestinal permeability were quantified.
  
  
  RESULTS
  There was increased MSC engraftment into injured compared to uninjured intestine for all experimental groups, with significantly increased engraftment for AF-MSC+HB-EGF compared to AF-MSC alone. Administration of HB-EGF and MSC improved intestinal histology and intestinal permeability after I/R injury. The greatest improvement was with combined administration of HB-EGF+AF-MSC.
  
  
  CONCLUSIONS
  Both HB-EGF alone and MSC alone can protect the intestines from I/R injury, with synergistic efficacy occurring when HB-EGF and AF-MSC are administered together.
authors.affiliation: The Research Institute at Nationwide Children's Hospital, Center for Perinatal Research, Columbus, OH 43205, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Watkins
authors.forename: Jixin
authors.initials: J
authors.lastname: Yang
authors.forename: Mika A B
authors.initials: MA
authors.lastname: Matthews
authors.forename: Gail E
authors.initials: GE
authors.lastname: Besner
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology; D000818:Animals; D001854:Bone Marrow Cells; D003131:Combined Modality Therapy; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000627:therapeutic use*; D007421:Intestine, Small / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D020011:Protective Agents / Q000627:therapeutic use*; D011897:Random Allocation; D015427:Reperfusion Injury / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D005765:Gastrointestinal Agents; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D020011:Protective Agents
keywords: Amniotic fluid; Bone marrow; Heparin-binding EGF-like growth factor; Intestinal injury; Ischemia/reperfusion; Mesenchymal stem cells