Terrence M Rager1, Jacob K Olson2, Yu Zhou2, Yijie Wang2, Gail E Besner3. 1. Center for Perinatal Research, the Research Institute at Nationwide Children's Hospital, Columbus, OH; The Ohio State University College of Medicine, Columbus, OH. 2. Center for Perinatal Research, the Research Institute at Nationwide Children's Hospital, Columbus, OH. 3. Department of Pediatric Surgery, Nationwide Children's Hospital, Columbus, OH; Center for Perinatal Research, the Research Institute at Nationwide Children's Hospital, Columbus, OH. Electronic address: Gail.Besner@NationwideChildrens.org.
Abstract
PURPOSE: Treatment options for necrotizing enterocolitis (NEC) remain inadequate. Bone marrow-derived mesenchymal stem cells (BM-MSCs) can protect the intestines from NEC. Exosomes are nanoparticle-sized vesicles with important cell signaling capabilities. The objective of this study was to determine whether BM-MSC-derived exosomes can prevent NEC. METHODS: Rat pups were either breast fed (Group 1) or subjected to experimental NEC and randomized to receive either no treatment (Group 2) or an intraperitoneal (IP) injection of PBS (Group 3), BM-MSC (Group 4), or BM-MSC-derived exosomes (Group 5). Histologic injury grade and intestinal permeability were determined. The effect of BM-MSC-derived exosomes on IEC-6 intestinal epithelial cells in an in vitro scrape model of wound healing was also determined. RESULTS: Animals exposed to NEC that were either untreated or received PBS alone had an NEC incidence of 46% and 41%, respectively (p=0.61). Compared to untreated pups, the incidence of NEC was significantly lower in pups treated with either BM-MSC (9%, p=0.0003) or MB-MSC-derived exosomes (13%, p=0.0008). Similar results were found for intestinal permeability. Wound healing in IEC-6 cells was significantly increased by BM-MSC-derived exosomes. CONCLUSION: BM-MSC-derived exosomes protect the intestines from NEC and may represent a novel, cell-free, preventative therapy for NEC in the future.
PURPOSE: Treatment options for necrotizing enterocolitis (NEC) remain inadequate. Bone marrow-derived mesenchymal stem cells (BM-MSCs) can protect the intestines from NEC. Exosomes are nanoparticle-sized vesicles with important cell signaling capabilities. The objective of this study was to determine whether BM-MSC-derived exosomes can prevent NEC. METHODS:Rat pups were either breast fed (Group 1) or subjected to experimental NEC and randomized to receive either no treatment (Group 2) or an intraperitoneal (IP) injection of PBS (Group 3), BM-MSC (Group 4), or BM-MSC-derived exosomes (Group 5). Histologic injury grade and intestinal permeability were determined. The effect of BM-MSC-derived exosomes on IEC-6 intestinal epithelial cells in an in vitro scrape model of wound healing was also determined. RESULTS: Animals exposed to NEC that were either untreated or received PBS alone had an NEC incidence of 46% and 41%, respectively (p=0.61). Compared to untreated pups, the incidence of NEC was significantly lower in pups treated with either BM-MSC (9%, p=0.0003) or MB-MSC-derived exosomes (13%, p=0.0008). Similar results were found for intestinal permeability. Wound healing in IEC-6 cells was significantly increased by BM-MSC-derived exosomes. CONCLUSION: BM-MSC-derived exosomes protect the intestines from NEC and may represent a novel, cell-free, preventative therapy for NEC in the future.
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