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Mesenchymal Stromal Cell Derived Extracellular Vesicles Reduce Hypoxia-lschaemia Induced Perinatal Brain Injury

Sisa, C; Kholia, S; Naylor, J; Sanchez, MBH; Bruno, S; Deregibus, MC; Camussi, G; ... Hristova, M; + view all (2019) Mesenchymal Stromal Cell Derived Extracellular Vesicles Reduce Hypoxia-lschaemia Induced Perinatal Brain Injury. Frontiers in Physiology , 10 , Article 282. 10.3389/fphys.2019.00282. Green open access

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Abstract

Background: Neonatal hypoxic-ischemic (HI) insult is a leading cause of disability and death in newborns, with therapeutic hypothermia being the only currently available clinical intervention. Thus there is a great need for adjunct and novel treatments for enhanced or alternative post-HI neuroprotection. Extracellular vesicles (EVs) derived from mesenchymal stromal/stem cells (MSCs) have recently been shown to exhibit regenerative effects in various injury models. Here we present findings showing neuroprotective effects of MSC-derived EVs in the Rice–Vannucci model of severe HI-induced neonatal brain insult. Methods: Mesenchymal stromal/stem cell-derived EVs were applied intranasally immediately post HI-insult and behavioral outcomes were observed 48 h following MSC-EV treatment, as assessed by negative geotaxis. Brains were thereafter excised and assessed for changes in glial responses, cell death, and neuronal loss as markers of damage at 48 h post HI-insult. Results: Brains of the MSC-EV treated group showed a significant decrease in microglial activation, cell death, and percentage tissue volume loss in multiple brain regions, compared to the control-treated groups. Furthermore, negative geotaxis test showed improved behavioral outcomes at 48 h following MSC-EV treatment. Conclusion: Our findings highlight the clinical potential of using MSC-derived EVs following neonatal hypoxia-ischaemia.

Type: Article
Title: Mesenchymal Stromal Cell Derived Extracellular Vesicles Reduce Hypoxia-lschaemia Induced Perinatal Brain Injury
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fphys.2019.00282
Publisher version: https://doi.org/10.3389/fphys.2019.00282
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Science & Technology, Life Sciences & Biomedicine, Physiology, hypoxia, ischaemia, extracellular vesicles, mesenchymal stromal/stem cells, microglia, neuroprotection, CEREBRAL-ARTERY OCCLUSION, NEURAL PROGENITOR CELLS, WHITE-MATTER INJURY, LOW-BIRTH-WEIGHT, STEM-CELLS, SELECTIVE VULNERABILITY, NEONATAL ENCEPHALOPATHY, DRUG-DELIVERY, ISCHEMIA, TERM
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10072435
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