Courtney Pisano1, Jeffrey Galley1, Mostafa Elbahrawy1, Yijie Wang1, Aidan Farrell1, David Brigstock1, Gail E Besner2. 1. Department of Pediatric Surgery, Center for Perinatal Research Nationwide Children's Hospital, Columbus, OH. 2. Department of Pediatric Surgery, Center for Perinatal Research Nationwide Children's Hospital, Columbus, OH. Electronic address: gail.besner@nationwidechildrens.org.
Abstract
PURPOSE: Necrotizing enterocolitis (NEC) is a leading cause of death in premature infants. Breast feeding decreases the incidence of NEC but, even with aggressive promotion of nursing in Neonatal Intensive Care Units, morbidity and mortality remain high. Previous studies from our laboratory have demonstrated that extracellular vesicles (EVs) purified from mouse and rat stem cells can protect the intestines from NEC. The aim of this study was to determine whether human breast milk (BM)-derived EVs could prevent NEC. METHODS: EVs were purified from human donor breast milk. NEC was induced in premature rat pups by exposure to asphyxia/hypothermia/hypercaloric feeds. Pups were randomized to: (1) breast fed, no injury, (2) NEC, (3) NEC + BM-derived EVs once intraperitoneally (IP), (4) NEC + BM-derived EVs enterally (PO) with each feed. Intestinal tracts were examined for histologic damage. Additionally, the effect of BM-derived EVs on intestinal epithelial cells (IEC) subjected to hypoxia/reoxygenation injury in vitro was examined. RESULTS: NEC incidence was 0% in breast-fed pups and 62% in pups subjected to NEC. IP administration of BM-derived EVs decreased NEC incidence to 29% and enteral administration further decreased NEC incidence to 11.9%. (p < 0.05). BM-derived EVs significantly increased cell proliferation and decreased apoptosis in IEC in vitro. CONCLUSION: Breast milk-derived EVs delivered either IP or enterally significantly decrease the incidence and severity of experimental NEC, protect IEC from injury in vitro, and may represent an innovative therapeutic option for NEC in the future. TYPE OF STUDY: Basic science study. LEVEL OF EVIDENCE: N/A.
PURPOSE:Necrotizing enterocolitis (NEC) is a leading cause of death in premature infants. Breast feeding decreases the incidence of NEC but, even with aggressive promotion of nursing in Neonatal Intensive Care Units, morbidity and mortality remain high. Previous studies from our laboratory have demonstrated that extracellular vesicles (EVs) purified from mouse and rat stem cells can protect the intestines from NEC. The aim of this study was to determine whether human breast milk (BM)-derived EVs could prevent NEC. METHODS: EVs were purified from humandonor breast milk. NEC was induced in premature rat pups by exposure to asphyxia/hypothermia/hypercaloric feeds. Pups were randomized to: (1) breast fed, no injury, (2) NEC, (3) NEC + BM-derived EVs once intraperitoneally (IP), (4) NEC + BM-derived EVs enterally (PO) with each feed. Intestinal tracts were examined for histologic damage. Additionally, the effect of BM-derived EVs on intestinal epithelial cells (IEC) subjected to hypoxia/reoxygenation injury in vitro was examined. RESULTS:NEC incidence was 0% in breast-fed pups and 62% in pups subjected to NEC. IP administration of BM-derived EVs decreased NEC incidence to 29% and enteral administration further decreased NEC incidence to 11.9%. (p < 0.05). BM-derived EVs significantly increased cell proliferation and decreased apoptosis in IEC in vitro. CONCLUSION: Breast milk-derived EVs delivered either IP or enterally significantly decrease the incidence and severity of experimental NEC, protect IEC from injury in vitro, and may represent an innovative therapeutic option for NEC in the future. TYPE OF STUDY: Basic science study. LEVEL OF EVIDENCE: N/A.
Authors: Christopher J McCulloh; Jacob K Olson; Yijie Wang; Jennifer Vu; Sarah Gartner; Gail E Besner Journal: J Surg Res Date: 2017-03-31 Impact factor: 2.192
Authors: Ilse H de Lange; Charlotte van Gorp; Laurens D Eeftinck Schattenkerk; Wim G van Gemert; Joep P M Derikx; Tim G A M Wolfs Journal: Nutrients Date: 2021-05-19 Impact factor: 5.717
Authors: Yijie Wang; Robert M Jaggers; Pamela Mar; Jeffrey D Galley; Terri Shaffer; Adrian Rajab; Shivani Deshpande; Lauren Mashburn-Warren; John R Buzzo; Steven D Goodman; Michael T Bailey; Gail E Besner Journal: Brain Behav Immun Health Date: 2021-04-06