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

J Pediatr Surg. 2014 Jun;49(6):938-44; discussion 944. doi: 10.1016/j.jpedsurg.2014.01.030. Epub 2014 Jan 31.

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.

Keywords: Amniotic fluid; Bone marrow; Heparin-binding EGF-like growth factor; Intestinal injury; Ischemia/reperfusion; Mesenchymal stem cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cells, Cultured
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Heparin-binding EGF-like Growth Factor / biosynthesis
  • Heparin-binding EGF-like Growth Factor / genetics
  • Heparin-binding EGF-like Growth Factor / pharmacology*
  • Intestines / blood supply*
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Pregnancy
  • Pregnancy, Animal*
  • RNA, Messenger / genetics
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / therapy*

Substances

  • Heparin-binding EGF-like Growth Factor
  • RNA, Messenger