Exosomes Derived from Adipose Mesenchymal Stem Cells Carrying miRNA-22-3p Promote Schwann Cells Proliferation and Migration through Downregulation of PTEN

Abstract

Peripheral nerve injury (PNI) is often resulting from trauma, which leads to severe and permanently disability. Schwann cells are critical for facilitating the regeneration process after PNI. Adipose-derived mesenchymal stem cells (ADSCs) exosomes have been used as a novel treatment for peripheral nerve injury. However, the underlying mechanism remains unclear. In this study, we isolated ADSCs and extracted exosomes, which were verified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot (WB). Cocultured with Dorsal Root Ganglion (DRG) and Schwann cells (SCs) to evaluate the effect of exosomes on the growth of DRG axons by immunofluorescence, and the proliferation and migration of SCs by CCK8 and Transwell assays, respectively. Through exosomal miRNA sequencing and bioinformatic analysis, the related miRNAs and target gene were predicted and identified by dual luciferase assay. Related miRNAs were overexpressed and inhibited, respectively, to clarify their effects; the downstream pathway through the target gene was determined by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and WB. Results found that ADSC-exosomes could promote the proliferation and migration of SCs and the growth of DRG axons, respectively. Exosomal miRNA-22-3p from ADSCs directly inhibited the expression of Phosphatase and Tensin Homolog deleted on Chromosome 10 (PTEN), activated phosphorylation of the AKT/mTOR axis, and enhanced SCs proliferation and migration. In conclusion, our findings suggest that ADSC-exosomes could promote SCs function through exosomal miRNA-22-3p, which could be used as a therapeutic target for peripheral nerve injury.

Stem cell-derived extracellular vesicle-based therapy for nerve injury: A review of the molecular mechanisms

“…Recently, it has been documented that adipose mesenchymal stem cell-derived exosomes carrying miRNA-22–3p promote Schwann cell proliferation and migration as well as dorsal root ganglion axon growth through downregulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). 61 …”

Applications of Stem Cell-Derived Extracellular Vesicles in Nerve Regeneration

“…However, miRNAs are known to play a role in Schwann cells’ proliferation and myelin regeneration. By knocking out ADSC-derived exosomes overexpressing miR-22-3p, we found that its effects on chromosome 10 (PTEN) activated the PI3K/Akt signaling pathway and contributed to the repair of the recurrent laryngeal nerve as well as the proliferation of Schwann cells [ 121 , 122 ].…”

MicroRNA-21a-5p-modified macrophage exosomes as natural nanocarriers promote bone regeneration by targeting GATA2

“…However, the mechanisms controlling the beneficial effects of M1 macrophage exosomes in the context of osteoblast differentiation are still unknown. It has been demonstrated that exosomes can translocate enriched miRNAs to target cells and perform their functions by binding to the 3′ untranslated regions (UTR) of intracellular mRNAs leading to translational repression or target degradation [ 27 ]. Herein, we present evidence that M1 macrophage-derived exosome miR-21a-5p is targeted to GATA2 to promote bone healing.…”