Pulsed electromagnetic field stimulation enhances neurite outgrowth in neural cells and modulates inflammation in macrophages

Nerve regeneration following traumas remains an unmet challenge.The application of pulsed electromagnetic field(PEMF)stimulation has gained traction for a minimally invasive regeneration of nerves.However,a sys-tematic exploration of different PEMF parameters influencing neuron function at a cellular level is not available.In this study,we exposed neuroblastoma F11 cells to PEMF to trigger beneficial effects on neurite outgrowth.Different carrier frequencies,pulse repetition frequencies,and duty cycles were screened with a custom ad hoc setup to find the most influential parameters values.A carrier frequency of 13.5 MHz,a pulse repetition frequency of 20 Hz,and a duty cycle of 10%allowed maximal neurite outgrowth,with unaltered viability with respect to non-stimulated controls.Furthermore,in a longer-term analysis,such optimal conditions were also able to in-crease the gene expression of neuronal expression markers NeuN and Tuj-1 and transcription factor Ngn1.Finally,the same optimal stimulation conditions were also applied to THP-1 macrophages,and both pro-inflammatory(TNF-α,IL-1β,IL-6,IL-8)and anti-inflammatory cytokines(IL-10,CD206)were analyzed.The optimal PEMF stimulation parameters did not induce differentiation towards an M1 macrophage phenotype,decreased IL-1β and IL-8 gene expression,decreased TNF-α and IL-8 cytokine release in M1-differentiated cells,increased IL-10 and CD206 gene expression,as well as IL-10 cytokine release in M0 cells.The specific PEMF stimulation regime,which is optimal in vitro,might have a high potential for a future in vivo translation targeting neural regeneration and anti-inflammatory action for treating peripheral nerve injuries.

Ultrasound-triggered three dimensional hyaluronic acid hydrogel promotes in vitro and in vivo reprogramming into induced pluripotent stem cells

Cellular reprogramming technologies have been developed with different physicochemical factors to improve the reprogramming efficiencies of induced pluripotent stem cells(iPSCs).Ultrasound is a clinically applied noncontact biophysical factor known for regulating various cellular behaviors but remains uninvestigated for cellular reprogramming.Here,we present a new reprogramming strategy using low-intensity ultrasound(LIUS)to improve cellular reprogramming of iPSCs in vitro and in vivo.Under 3D microenvironment conditions,increased LIUS stimulation shows enhanced cellular reprogramming of the iPSCs.The cellular reprogramming process facilitated by LIUS is accompanied by increased mesenchymal to epithelial transition and histone modification.LIUS stimulation transiently modulates the cytoskeletal rearrangement,along with increased membrane fluidity and mobility to increase HA/CD44 interactions.Furthermore,LIUS stimulation with HA hydrogel can be utilized in application of both human cells and in vivo environment,for enhanced reprogrammed cells into iPSCs.Thus,LIUS stimulation with a combinatorial 3D microenvironment system can improve cellular reprogramming in vitro and in vivo environments,which can be applied in various biomedical fields.