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-temati...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.展开更多
文摘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.