Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization

• Published in: Cellular physiology and biochemistry Vol. 47; no. 2; pp. 864 - 878
• Main Authors: Jiang, Mei, Wang, Hairong, Jin, Mingming, Yang, Xuelian, Ji, Haifeng, Jiang, Yufeng, Zhang, Hanwen, Wu, Feifei, Wu, Guolu, Lai, Xiaoyin, Cai, Liying, Hu, Rongguo, Xu, Limin, Li, Longxuan
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 2018; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: Acute ischemic stroke; Adipose Tissue - cytology; Aged; Animals; Apoptosis; Autophagy; Autophagy-Related Protein 5 - chemistry; Autophagy-Related Protein 5 - genetics; Autophagy-Related Protein 5 - metabolism; Brain Injuries - metabolism; Brain Injuries - pathology; Cardiovascular disease; Cytokines - blood; Ethics; Exosome; Exosomes - metabolism; Female; Hospitals; Humans; Infections; Ischemia; Laboratory animals; Macrophages - cytology; Macrophages - metabolism; Male; Mice; Microglia - cytology; Microglia - metabolism; Microglial/macrophage polarization; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; MiR-30d-5p; Original Paper; Rats; Rats, Sprague-Dawley; Rodents; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Stroke; Stroke - metabolism; Stroke - pathology; Transplants & implants; Traumatic brain injury; Tumor necrosis factor-TNF; China; MiR-30d-5p; Acute ischemic stroke; Microglial/macrophage polarization; Exosome; Autophagy
• ISSN: 1015-8987; 1421-9778; 1421-9778
• DOI: 10.1159/000490078

Background/Aims: Recent studies have indicated that exosomes secreted from adipose-derived stem cells (ADSCs) have important effects in the treatment of ischemic injury. However, the treatment mechanism is unclear. This study aimed to investigate whether ADSC-derived exosomes enriched with microRNA (miR)-30d-5p have a protective effect on acute ischemic stroke (AIS). Methods: In the current study, inflammatory factors and miR-30d-5p expression were assessed in 70 subjects with AIS and 35 healthy controls. Exosomes were characterized by transmission electron microscopy and further examined using nanoparticle tracking analyses. A rat model of AIS and an in vitro model of oxygen- and glucose-deprived (OGD) primary microglia were established to study the protective mechanism of exosomes from miR-30d-5p-overexpressing ADSCs in ischemia-induced nerve injury. Results: The results showed that following AIS, the expression of inflammatory cytokines increased, while the anti-inflammatory cytokines IL-4, IL-10, and miR-30d-5p decreased both in patients and in animal models. Moreover, in vitro studies demonstrated that suppression of autophagy significantly reduced the OGD-induced inflammatory response. In addition, exosome treatment was more effective in suppressing the inflammatory response by reversing OGD-induced and autophagy-mediated microglial polarization to M1. Furthermore, in vivo studies showed that exosomes derived from ADSCs significantly decreased the cerebral injury area of infarction by suppressing autophagy and promoting M2 microglia/macrophage polarization. Conclusions: Our results suggest that miR-30d-5p-enhanced ADSC-derived exosomes prevent cerebral injury by inhibiting autophagy-mediated microglial polarization to M1.