title: Exosomes secreted from bone marrow-derived mesenchymal stem cells protect the intestines from experimental necrotizing enterocolitis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  BM-MSC-derived exosomes protect the intestines from NEC and may represent a novel, cell-free, preventative therapy for NEC in the future.
authors.affiliation: Center for Perinatal Research, the Research Institute at Nationwide Children's Hospital, Columbus, OH; The Ohio State University College of Medicine, Columbus, OH.
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Rager
authors.affiliation: Center for Perinatal Research, the Research Institute at Nationwide Children's Hospital, Columbus, OH.
authors.forename: Jacob K
authors.initials: JK
authors.lastname: Olson
authors.affiliation: Center for Perinatal Research, the Research Institute at Nationwide Children's Hospital, Columbus, OH.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Center for Perinatal Research, the Research Institute at Nationwide Children's Hospital, Columbus, OH.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Gail E
authors.initials: GE
authors.lastname: Besner
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000517:prevention & control*; D055354:Exosomes / Q000378:metabolism / Q000637:transplantation*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D059630:Mesenchymal Stem Cells / Q000473:pathology; D010539:Permeability; D020011:Protective Agents; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020011:Protective Agents
keywords: Exosomes; Mesenchymal stem cells; NEC; Necrotizing enterocolitis