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

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.

exosome; induced pluripotent stem cell; lncRNA; neuroinflammation.