Few-Layered Conductive Graphene Foams for Electrical Transdifferentiation of Mesenchymal Stem Cells Into Schwann Cell-Like Phenotypes

This study investigates the potential of few-layered conductive graphene foams as 3D platforms for the electrical transdifferentiation of mesenchymal stem cells (MSCs) into Schwann cell (SC)-like phenotypes for peripheral nerve injury (PNI) treatment. The 3D graphene foams (3D-GF) are cytocompatible with MSCs and created a favorable microenvironment for the cells to attach, grow, proliferate, and transdifferentiate. We demonstrated that MSCs cultured within 3D-GF can be transdifferentiated into SC-like phenotypes using the synergistic effects of electrical stimulation and 3D porous and conductive structure. Our immunocytochemistry and gene expression analyses showed the expression of Schwann cell markers and enhanced secretion of growth factors, suggesting successful transdifferentiation of MSCs into SC-like phenotypes upon electrical stimulation. Our degree of transdifferentiation results (∼90% by electrical) are comparable with conventionally used chemical stimuli-based transdifferentiation protocols (∼85% by chemical). The secreted growth factors are also biologically active, showing enhanced neurite outgrowth in PC12TrkB cells compared to the control. Our transcriptomics results also showed that the electrical stimulation-directed transdifferentiation mainly occurs through MAPK signaling pathway activation. These findings suggest that conductive 3D-GF could serve as a promising platform for peripheral nerve regeneration applications, offering a novel approach to enhance the transdifferentiation and functional properties of MSCs.