MSC-derived small extracellular vesicles alleviate diabetic retinopathy by delivering miR-22-3p to inhibit NLRP3 inflammasome activation

Quick Facts

  • Publication title: MSC-derived small extracellular vesicles alleviate diabetic retinopathy by delivering miR-22-3p to inhibit NLRP3 inflammasome activation
  • Journal: Stem Cells
  • Year: 2023
  • DOI: 10.1093/stmcls/sxad078
  • PMID/PMCID: 37847598

Research overview

This study aimed to investigate the effect of mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) on diabetic retinopathy (DR) and its underlying mechanism. Our findings indicate that MSC-sEVs might be a potential therapeutic method for DR.

Key findings

In vivo, MSC-sEVs inhibited NLRP3 inflammasome activation, suppressed microglial activation, decreased inflammatory cytokines levels in the retina, and alleviated DR as evidenced by improved histological morphology and blood-retinal barrier function.

Based on miRNA sequencing of MSC-sEVs, bioinformatic software, and dual-luciferase reporter assay, miR-22-3p stood out as the critical molecule for the role of MSC-sEVs in regulating NLRP3 inflammasome activation.

Diabetic rats had lower level of miR-22-3p in their retina than those of control and sEV-treated rats.

Confocal microscopy revealed that sEV could be internalized by microglia both in vivo and in vitro.

Study design

In vivo, MSC-sEVs were injected intravitreally into diabetic rats to determine the therapeutic efficacy.

In vitro, MSC-sEVs with/without miR-22-3p inhibition were cocultured with advanced glycation end-products (AGEs)-induced microglia with/without NLRP3 overexpression to explore the molecular mechanism.

Echo Biotech Role

Echo Biotech contributed miRNA profiling/sequencing and bioinformatic analysis.

Related platforms: Exoomics®

Related services and capabilities: EV miRNA Profiling / Sequencing

References

Original publication: MSC-derived small extracellular vesicles alleviate diabetic retinopathy by delivering miR-22-3p to inhibit NLRP3 inflammasome activation Stem Cells. 2023. DOI: 10.1093/stmcls/sxad078. PMID/PMCID: 37847598.