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HB-EGF augments the ability of mesenchymal stem cells to attenuate intestinal injury

  • Daniel J. Watkins
    Affiliations
    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
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  • Yu Zhou
    Affiliations
    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
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  • Mika A.B. Matthews
    Affiliations
    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
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  • Li Chen
    Affiliations
    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
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  • Gail E. Besner
    Correspondence
    Corresponding author at: Department of Pediatric Surgery, Nationwide Children’s Hospital, ED 383, 700 Children’s Drive, Columbus, OH 43205. Tel.: +1 614 722 3900; fax: +1 614 722 3903.
    Affiliations
    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
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Published:February 03, 2014DOI:https://doi.org/10.1016/j.jpedsurg.2014.01.030

      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.

      Key words

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