Extremely low frequency electromagnetic fields enhance neuronal differentiation of human mesenchymal stem cells on graphene-based substrates

Graphene is a non-cytotoxic and biocompatible material which serves as a powerful platform for cell growth, differentiation, and fate conversion. The unique features of this nanomaterial are exploited in regenerative medicine and tissue engineering as a scaffold for biological tissues. Graphene-based substrates support neuronal differentiation of stem cells and hence can potentially be applied in nerve regeneration. Since the exact differentiation mechanism mediated by graphene substrate is not fully understood, the efficiency of the process remains to be improved. Herein, the extremely low frequency electromagnetic fields (ELF-EMF; 50 Hz, 1 mT) exposure synergistically increased biological efficacy of neuronal differentiation in bone marrow-derived human mesenchymal stem cells (hMSCs) grown on graphene-coated substrate. We show that such enhancement in neurogenesis is achieved by altering global gene expression profile thereby up-regulating cell adhesion through intracellular calcium influx and activated focal adhesion kinase signaling pathway, which is stimulated by extracellular matrix production. Our findings may provide the framework for a useful therapeutic strategy in regenerative medicine.