Heparin-binding EGF-like growth factor and enteric neural stem cell transplantation in the prevention of experimental necrotizing enterocolitis in mice

Abstract

BackgroundNecrotizing enterocolitis (NEC) is associated with loss of neurons and glial cells in the enteric nervous system (ENS). Our goal was to determine whether enteric neural stem cell (NSC) transplantation, in conjunction with heparin binding-epidermal growth factor-like growth factor (HB-EGF), could protect against experimental NEC.MethodsIn vitro, HB-EGF effect on NSC proliferation and migration, and the receptors utilized by HB-EGF to exert these effects, were determined. In vivo, mouse pups were exposed to experimental NEC and treated with either NSC alone, HB-EGF alone, NSC+HB-EGF, or HB-EGF over-expressing NSC. NSC engraftment and differentiation into neurons in the ENS, intestinal injury, intestinal permeability and intestinal motility were determined.ResultsHB-EGF promotes NSC proliferation via ErbB-1 receptors and enhances NSC migration via ErbB-1, ErbB-4 and Nardilysin receptors. HB-EGF significantly enhanced the engraftment of transplanted NSC into the ENS during NEC. NSC transplantation significantly reduced NEC incidence and improved gut barrier function and intestinal motility, and these effects were augmented by simultaneous administration of HB-EGF or by transplantation of HB-EGF-over-expressing NSC.ConclusionsHB-EGF promotes NSC proliferation and migration. HB-EGF and NSC reduce intestinal injury and improve gut barrier function and intestinal motility in experimental NEC. Combined HB-EGF and NSC transplantation may represent a potential future therapy to prevent NEC.

Exosomes secreted from bone marrow-derived mesenchymal stem cells protect the intestines from experimental necrotizing enterocolitis

“…In addition, the current studies exclusively examined exosomes derived from BM-MSC. We have previously shown that neural stem cells (NSC) can also protect the intestines from NEC [38]. Future studies will examine the efficacy of exosomes derived from different types of stem cells, including NSC and amniotic fluid (AF)-derived MSC.…”

Stem cells and necrotizing enterocolitis: A direct comparison of the efficacy of multiple types of stem cells

“…(6, 17–19) Intestine from duodenum to ileum was harvested, opened longitudinally, and the mucosa and submucosa stripped away. The muscular layer was digested in DMEM/F12 containing 1mg/mL Collagenase and 1mg/mL Dispase (Worthington Biochemical Corporation, Lakewood, NJ) for 45 – 60 min.…”

“…The model of NEC was based on that described by Barlow et al . (6, 7, 20–23) Rat pups delivered via C-section one half-day prematurely were randomized into six groups: (1) breastfed ( n = 10 ); (2) NEC + 1% phosphate-buffered saline (PBS, Corning, Manassas, VA) ( n = 62 ); (3) NEC + AF-MSC ( n = 42 ); (4) NEC + AF-NSC ( n = 37 ); (5) NEC + BM-MSC ( n = 48 ); (6) NEC + E-NSC ( n = 36 ). After delivery, each pup received a single intraperitoneal (IP) injection of 2×10 6 SC in 0.1mL PBS.…”

Current Research on the Epidemiology, Pathogenesis, and Management of Necrotizing Enterocolitis

“…Recent evidence from 3 different research groups has suggested that stem cells are able to influence the course of the disease in experimental NEC [88]: amniotic fluid stem (AFS) cells [89], mesenchymal stem cells [90,91], and enteric neural stem system cells [92]. In addition to the beneficial effects of AFS cells and the conditioned medium from AFS cells, other recent evidence highlights the potential role of factors in amniotic fluid in the prevention and/or treatment of NEC.…”