Synergistic effects of HB-EGF and mesenchymal stem cells in a murine model of intestinal ischemia/reperfusion injury

J Pediatr Surg. 2013 Jun;48(6):1323-9. doi: 10.1016/j.jpedsurg.2013.03.032.

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.

Materials and 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.

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

Publication types

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

MeSH terms

  • Amniotic Fluid / cytology
  • Animals
  • Bone Marrow Cells
  • Combined Modality Therapy
  • Female
  • Gastrointestinal Agents / therapeutic use*
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins / therapeutic use*
  • Intestine, Small* / pathology
  • Intestine, Small* / physiopathology
  • Intestine, Small* / surgery
  • Male
  • Mesenchymal Stem Cell Transplantation* / methods
  • Mice
  • Mice, Inbred C57BL
  • Protective Agents / therapeutic use*
  • Random Allocation
  • Reperfusion Injury / therapy*
  • Treatment Outcome

Substances

  • Gastrointestinal Agents
  • Hbegf protein, mouse
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Protective Agents