Exosomes secreted from induced pluripotent stem cell ameliorate the lipopolysaccharide induced neuroinflammatory response via lncRNA‐0949

Abstract

Abstract Purpose To study the effect of exosomes derived from the induced pluripotent stem cells (iPSCs) in the neuroinflammatory response of microglia caused by lipopolysaccharide (LPS) and reveal the potential underlying mechanism. Methods A permanent microglia cell line HMO6 was activated by LPS. The features of exosomes were analyzed by nano flow cytometry, Western blot and transmission electron microscope. The RNA‐seq was used to analyze the difference of noncoding RNA profiles between iPSC‐Exos and HMO6 derived exosomes and proved that long no‐coding RNA (lncRNA‐0949) was highly expressed in the iPSC‐Exos. Activated HMO6 cells were cocultured with iPSC‐Exos in which lncRNA‐0949 was overexpressed, knocked down or normally expressed. Quantitative real‐time polymerase chain reaction (RT‐qPCR), Enzyme‐Linked Immunosorbent Assay and Western blot assay were adopted to analyze RNA and protein expression of inflammatory factors in HMO6 cells. Results The oxidative stress and inflammatory response of microglia were significantly attenuated with the iPSC derived exosomes treatment. LncRNA‐0949 was effectively delivered into the HMO6 cells through the iPSC‐Exos, which largely alleviated the production of malondialdehyde, IL‐6, IL‐1β and TNF‐α in HMO6 cells. Overexpression of lncRNA‐0949 could enhance the anti‐inflammatory effect of the iPSC‐Exos, and knock‐down of lncRNA‐0949 impaired this availability. Conclusion According to our results, lncRNA‐0949 enriched exosomes from iPSC could potentially be used as a therapeutic strategy to prevent/treat neuroinflammatory diseases.

Keywords

• exosome
• induced pluripotent stem cell
• lncRNA
• neuroinflammation