Exosomes derived from human umbilical cord mesenchymal stem cells loaded with RVG-Lamp2b and Netrin-1 promotes Schwann cell invasion and migration

BACKGROUND: Netrin-1 has a neuroprotective effect by regulating angiogenesis, autophagy, apoptosis, and neuroinflammation. This study investigated the effects of netrin-1 delivery to mouse Schwann cells and vascular endothelial cells using exosomes modified with rabies virus glycoprotein (RVG) peptides. MATERIALS AND METHODS: RVG-Lamp2b and/or Netrin-1 were overexpressed in human umbilical cord mesenchymal stem cells to obtain exosomes modified with RVG-Lamp2b and/or loaded with Netrin-1. Then, exosomes were labeled with carboxyfluorescein diacetate succinimidyl ester and co-cultured with mouse Schwann cells and endothelial cells. Netrin-1 expression in Schwann cells and endothelial cells was measured using quantitative polymerase chain reaction and immunoblotting. Moreover, methyl thiazolyl tetrazolium assays and Transwell assays were used to detect proliferation, migration, and invasion of Schwann cells and endothelial cells. RESULTS: Exosomes with RVG-Lamp2b entered Schwann cells more readily compared with the exosomes without RVG-Lamp2b. Meanwhile, this was not the case in endothelial cells. Netrin-1-loaded exosomes significantly promoted Netrin-1 expression, cell proliferation, migration, invasion, and epithelial-mesenchymal transition in Schwann cells and endothelial cells. These effects were further enhanced by Netrin-1-loaded exosomes modified with RVG-Lamp2b in Schwann cells, but not in endothelial cells. CONCLUSION: HucMSC-derived exosomes loaded with RVG-Lamp2b and Netrin-1 promote proliferation, migration, and invasion of Schwann cells.