Mesenchymal stem cell-derived exosomes rescue oxygen-glucose deprivation-induced injury in endothelial cells

• Published in: Current neurovascular research
• Main Authors: Kong, Li-Yun, Liang, Meng-Ya, Liu, Jian-Ping, Lai, Ping, Ye, Jun-Song, Zhang, Zu-Xiong, Du, Zhi-Ming, Yu, Jun-Jian, Gu, Liang, Xie, Fa-Chun, Tang, Zhi-Xian, Liu, Zi-You
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2020
• Subjects: Inflammatory factors; Brain; Exosome; Oxygen-glucose deprivation; Endothelial cells; Mesenchymal stem cells
• ISSN: 1875-5739
• DOI: 10.2174/1567202617666200214103950

The effects of mesenchymal stem cell (MSC)-derived exosomes on brain microvascular endothelial cells under oxygen-glucose deprivation (OGD), which mimics cells in deep hypothermic circulatory arrest (DHCA) in vitro, are yet to be studied. MSCs were co-cultured with primary rat brain endothelial cells, which were then exposed to OGD. Cell viability, apoptosis, the inflammatory factors (IL-1β, IL-6, and TNF-α), and the activation of inflammation-associated TLR4-mediated pyroptosis and the NF-κB signaling pathway were determined. Furthermore, exosomes derived from MSCs were isolated and incubated with endothelial cells to investigate whether the effect of MSCs is associated with MSC-derived exosomes. Apoptosis, cell viability, and the inflammatory response were also analyzed in OGD-induced endothelial cells incubated with MSC-derived exosomes. OGD treatment promoted endothelial cell apoptosis, induced the release of inflammatory factors IL-1β, IL-6, and TNF-α, and inhibited cell viability. Western blot analysis showed that OGD treatment induced TLR4, and NF-κB p65 subunit phosphorylation and caspase-1 upregulation, while co-culture with MSCs could reduce the effect of OGD treatment on endothelial cells. As expected, the effect of MSC-derived exosomes on OGD-treated endothelial cells was similar to that of MSCs. MSC-derived exosomes alleviated the OGD-induced decrease in the viability of endothelial cells, and increased levels of apoptosis, inflammatory factors, and the activation of inflammatory and inflammatory focal pathways. Both MSCs and MSC-derived exosomes attenuated OGD-induced rat primary brain endothelial cell injury. These findings suggest that at least some of the protective effects of MSCs on endothelial cells are mediated by MSC-derived exosomes.