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

• Main Authors: Claudia Sisa, Sharad Kholia, Jordan Naylor, Maria Beatriz Herrera Sanchez, Stefania Bruno, Maria Chiara Deregibus, Giovanni Camussi, Jameel M. Inal, Sigrun Lange, Mariya Hristova
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-03-01
• Series: Frontiers in Physiology
• Subjects: hypoxia; ischaemia; extracellular vesicles; mesenchymal stromal/stem cells; microglia; neuroprotection
• Online Access: https://www.frontiersin.org/article/10.3389/fphys.2019.00282/full

BackgroundNeonatal 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.MethodsMesenchymal 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.ResultsBrains 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.ConclusionOur findings highlight the clinical potential of using MSC-derived EVs following neonatal hypoxia-ischaemia.