Pulsed electromagnetic stimulation promotes neuronal maturation by up-regulating cholesterol biosynthesis

Pulsed electromagnetic fields (PEMFs) have emerged as a promising tool for enhancing neural differentiation of induced pluripotent stem cells (iPSCs). This study investigates the effects of PEMF stimulation on the neural differentiation of Ngn2-transduced human iPSCs. We demonstrated that PEMF exposure significantly upregulated cholesterol biosynthesis, promoting the expression of synaptic proteins such as synaptophysin and PSD95, while downregulating pluripotency-related genes. Functional assessments revealed that PEMF-treated iNs exhibited increased spontaneous calcium oscillations and enhanced action potential firing compared to controls. Electrophysiological analyses indicated improved resting membrane potential and action potential characteristics in PEMF-treated neurons. RNA sequencing highlighted significant alterations in gene expression associated with sterol metabolism and neural development. Our findings suggest that PEMF stimulation facilitates the neural differentiation of iPSCs by enhancing cholesterol biosynthesis, thereby promoting functional maturation and synaptic development in iNs. These results underscore the potential of PEMF as a therapeutic strategy in regenerative medicine for neurological disorders.