title: Heparin-binding epidermal growth factor-like growth factor and mesenchymal stem cells act synergistically to prevent experimental necrotizing enterocolitis.
abstract: BACKGROUND
  We have shown that administration of heparin-binding EGF (epidermal growth factor)-like growth factor (HB-EGF) protects the intestines from experimental necrotizing enterocolitis (NEC). We have also demonstrated that systemically administered mesenchymal stem cells (MSC) can engraft into injured intestines. This study investigated the effects of HB-EGF on MSC in vitro, and whether MSC and HB-EGF can act synergistically to prevent NEC in vivo.
  
  
  METHODS
  In vitro, the effect of HB-EGF on MSC proliferation, migration, and apoptosis was determined. In vivo, rat pups received MSC either intraperitoneally (IP) or intravenously (IV). Pups were assigned to 1 of 7 groups: Group 1, breast-fed; Group 2, experimental NEC; Group 3, NEC+HB-EGF; Group 4, NEC+MSC IP; Group 5, NEC+HB-EGF+MSC IP; Group 6, NEC+MSC IV; or Group 7, NEC+HB-EGF+MSC IV. Mesechymal stem cell engraftment, histologic injury, intestinal permeability, and mortality were determined.
  
  
  RESULTS
  Heparin-binding EGF-like growth factor promoted MSC proliferation and migration, and decreased MSC apoptosis in vitro. In vivo, MSC administered IV had increased engraftment into NEC-injured intestine compared with MSC administered IP (p < 0.05). Heparin binding EGF-like growth factor increased engraftment of IP-administered MSC (p < 0.01) and IV-administered MSC (p < 0.05). Pups in Groups 3 to 7 had a decreased incidence of NEC compared with nontreated pups (Group 2), with the lowest incidence in pups treated with HB-EGF+MSC IV (p < 0.01). Pups in Group 7 had a significantly decreased incidence of intestinal dilation and perforation, and had the lowest intestinal permeability, compared with other treatment groups (p < 0.01). Pups in all experimental groups had significantly improved survival compared with pups exposed to NEC, with the best survival in Group 7 (p < 0.05).
  
  
  CONCLUSIONS
  Heparin-binding EGF-like growth factor and MSC act synergistically to reduce injury and improve survival in experimental NEC.
authors: 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, OH, USA.
authors: Jixin
authors: J
authors: Yang
authors: Daniel
authors: D
authors: Watkins
authors: Chun-Liang
authors: CL
authors: Chen
authors: Bharath
authors: B
authors: Bhushan
authors: Yu
authors: Y
authors: Zhou
authors: Gail E
authors: GE
authors: Besner
mesh_terms: D000818:Animals; D020345:Enterocolitis, Necrotizing / Q000517:prevention & control*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C587883:HBEGF protein, human; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins