Low-intensity pulsed ultrasound upregulates pro-myelination indicators of Schwann cells enhanced by co-culture with adipose-derived stem cells.

Abstract

Peripheral nerve injuries are a common occurrence, resulting in considerable patient suffering; it also represents a major economic burden on society. To improve treatment options following peripheral nerve injuries, scientists aim to find a way to promote Schwann cell (SC) myelination to help nerves to carry out their functions effectively. In this study, we investigated myelination ability of SCs, regulated by co-culture with adipose-derived stem cells (ASCs) or low-intensity pulsed ultrasound (LIPUS), and synergistic effects of combined treatments. Schwann cells were co-cultured with or without ASCs, and either left untreated or treated with LIPUS for 10min/d for 1, 4 or 7days. Effects of LIPUS and ASC co-culture on pro-myelination indicators of SCs were analysed by real-time PCR (RT-PCR), Western blotting and immunofluorescence staining (IF). Our results indicate that ASC-SC co-culture and LIPUS, together or individually, promoted mRNA levels of epidermal growth factor receptor 3 (EGFR3/ErbB3), neuregulin1 (NRG1), early growth response protein 2 (Egr2/Krox20) and myelin basic protein (MBP), with corresponding increases in protein levels of ErbB3, NRG1 and Krox20. Interestingly, combination of ASC-SC co-culture and LIPUS displayed the most remarkable effects. We demonstrated that ASCs upregulated pro-myelination indicators of SCs by indirect contact (through co-culture) and that effects could be potentiated by LIPUS. We conclude that LIPUS, as a mechanical stress, may have potential in nerve regeneration with potential clinical relevance.