Journal
FRONTIERS IN PHYSIOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphys.2019.00282
Keywords
hypoxia; ischaemia; extracellular vesicles; mesenchymal stromal/stem cells; microglia; neuroprotection
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Funding
- BBSRC LIDo
- UCLB Apolo PoC
- UCL graduate school
- University of Westminster Start-Up Grant
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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.
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