TY - JOUR
T1 - Mesenchymal stromal cell derived extracellular vesicles reduce hypoxia-ischaemia induced perinatal injury
AU - Sisa, Claudia
AU - Kholia, Sharad
AU - Naylor, Jordan
AU - Herrera Sanchez, Maria Beatriz
AU - Bruno, Stefania
AU - Deregibus, Maria Chaiara
AU - Camussi, Giovanni
AU - Inal, Jameel
AU - Lange, Sigrun
AU - Hristova, Mariya
N1 - © 2019 Sisa, Kholia, Naylor, Herrera Sanchez, Bruno, Deregibus, Camussi, Inal, Lange and Hristova.
PY - 2019/3/19
Y1 - 2019/3/19
N2 - 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.
AB - 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.
KW - Mesenchymal Stem Cells
KW - Extracellular vesicles (EVs)
KW - Perinatal Brain Injury
KW - Ischaemia
KW - Neuroprotection
KW - Extracellular vesicles
KW - Hypoxia
KW - Mesenchymal stromal/stem cells
KW - Microglia
UR - http://www.scopus.com/inward/record.url?scp=85066424357&partnerID=8YFLogxK
U2 - 10.3389/fphys.2019.00282
DO - 10.3389/fphys.2019.00282
M3 - Article
SN - 1664-042X
VL - 10
SP - 282
JO - Frontiers in Physiology
JF - Frontiers in Physiology
IS - MAR
M1 - 282
ER -