Neurosci Lett. 2019 Jun 20:134346.

Nitrogen-doped carbon nanocages and human umbilical cord mesenchymal stem cells cooperatively inhibit neuroinflammation and protect against ischemic stroke.

Zhai L1, Maimaitiming Z2, Cao X3, Xu Y4, Jin J5.
Author information
Abstract
AIMS:
This study aimed to explore the synergistic effects of nitrogen-doped carbon nanocages (NCNCs) and human umbilical cord mesenchymal stem cells (HUC-MSCs) on ischemic stroke and investigate the potential underlying mechanisms.

MAIN METHODS:
The properties of NCNCs were analyzed by transmission electron microscopy, and the markers of HUC-MSCs were detected by flow cytometry. The cell toxicity of NCNCs was evaluated by MTT. Mice were induced cerebral infarction by transient middle cerebral artery occlusion (MCAO). NCNCs or HUC-MSCs or HUC-MSCs-NCNCs were intravenously injected thirty minutes after reperfusion. The infarct volume was examined by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and behavior tests were evaluated by the modified Neurological Severity Score (mNSS) and rotarod test. The mRNA levels of TNF-α and IL-10 were detected by real-time PCR. The protein levels of TNF-α stimulated gene/protein 6 (TSG-6) and prostaglandin 2 (PGE2) were detected by ELISA. The microglia markers (CD86 and CD206) and the protein levels of TNF-α and IL-10 were examined by flow cytometry. The protein levels of Iba1 and CD16 were determined by immunostaining.

KEY FINDINGS:
NCNCs enhanced the therapeutic effects of HUC-MSCs on MCAO mice, including reducing infarct volume, improving behavior scores and inhibiting inflammation response. In addition, NCNCs and HUC-MSCs cooperatively inhibit the mRNA and protein levels of TNF-α, and increased the mRNA and protein levels of IL-10 and protein levels of PGE2 and TSG-6 in LPS-treated microglia. Furthermore, NCNCs exerted synergistic effects with HUC-MSCs on remodeling microglia polarization.

SIGNIFICANCE:
NCNCs enhance the therapeutic effects of HUC-MSCs on cerebral infarction in a mouse MCAO model, and inhibit the microglia reactivation and neuroinflammation, which indicates it as a potential treatment for ischemic stroke.

Copyright ? 2019. Published by Elsevier B.V.

KEYWORDS:
HUC-MSCs; Ischemic stroke; NCNCs; Neuroinflammation; Synergistic effects

https://www.ncbi.nlm.nih.gov/pubmed/31229624