当前位置： SCI文献检索 > Acta Biomaterialia期刊下所有文献 > Mesenchymal stromal cell-derived extracellular vesicles modulate microglia/macrophage polarization and protect the brain against hypoxia-ischemic injury in neonatal mice by targeting delivery of miR-21a-5p.

Mesenchymal stromal cell-derived extracellular vesicles modulate microglia/macrophage polarization and protect the brain against hypoxia-ischemic injury in neonatal mice by targeting delivery of miR-21a-5p.

Abstract：

:Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) (MSC-EVs) exhibit protective effects in damaged or diseased tissues. However, the role of EVs secreted by MSC in hypoxia-ischemic (HI) injury in neonatal mice remains unknown. Systemic administration of MSC-EVs attenuated acute brain damage and neuroinflammation, and skewed CD11b+/CD45low microglia and CD11b+/CD45high brain monocyte/macrophage towards a more anti-inflammatory property as determined at 72 h post-HI. In addition, MSC-EVs remarkably improve the injury outcomes pups prior to weaning (P21), while no effect on long-term memory impairment (P42). Importantly, these effects were preceded by incorporation of MSC-EVs into a large number of neurons and microglia within HI group. Abundant levels of miR-21a-5p were present in EVs as determined with next-generation sequencing. Notably, MSC-EVs treatment further increased miR-21a-5p levels at 72 h post HI. Knockdown analyses revealed that miR-21a-5p, and its target-Timp3, were essential for this neuroprotective property of MSC-EVs following HI exposure as demonstrated in both in vitro and in vivo models. These findings suggest that a systemic administration of EVs derived from MSC, have the capacity to incorporated into neurons and microglia where they can then exert neuroprotection against HI-induced injury in neonates through the delivery of miR-21a-5p.

journal_name

Acta Biomater

journal_title

Acta biomaterialia

authors

Xin D,Li T,Chu X,Ke H,Yu Z,Cao L,Bai X,Liu D,Wang Z

doi

10.1016/j.actbio.2020.06.037

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

597-613

eissn

1742-7061

issn

1878-7568

pii

S1742-7061(20)30367-6

journal_volume

113

pub_type

杂志文章

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