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Optimization of Electrical Stimulation for Safe and Effective Guidance of Human Cells.

ABSTRACT: Direct current (DC) electrical stimulation has been shown to have remarkable effects on regulating cell behaviors. Translation of this technology to clinical uses, however, has to overcome several obstacles, including Joule heat production, changes in pH and ion concentration, and electrode products that are detrimental to cells. Application of DC voltages in thick tissues where their thickness is >0.8 mm caused significant changes in temperature, pH, and ion concentrations. In this study, we developed a multifield and -chamber electrotaxis chip, and various stimulation schemes to determine effective and safe stimulation strategies to guide the migration of human vascular endothelial cells. The electrotaxis chip with a chamber thickness of 1 mm allows 10 voltages applied in one experiment. DC electric fields caused detrimental effects on cells in a 1 mm chamber that mimicking 3D tissue with a decrease in cell migration speed and an increase in necrosis and apoptosis. Using the chip, we were able to select optimal stimulation schemes that were effective in guiding cells with minimal detrimental effects. This experimental system can be used to determine optimal electrical stimulation schemes for cell migration, survival with minimal detrimental effects on cells, which will facilitate to bring electrical stimulation for in vivo use.

SUBMITTER: Zhao Z

PROVIDER: S-EPMC8370347 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Vernakalant and electrical cardioversion for AF - Safe and effective.

Project description:AimsRapid restoration of sinus rhythm is an integral part of the management of recent-onset atrial fibrillation. We aimed to assess safety and efficacy of vernakalant, a multi-channel blocking agent, in combination with external electrical cardioversion.MethodsThis prospective cohort study comprised 230 patients (female 35%; median age 50 IQR 42-55) with recent-onset AF presenting to a university tertiary care center during a 6-year period. Management included intravenous vernakalant followed by electrical cardioversion in case of pharmacological failure.ResultsWithin 11 min (IQR 8-29), sinus rhythm could be restored by sole pharmacological management in 167 patients (73%). A left ventricular function lower than 55% (OR 3.51 (1.45-8.52)) and prior atrial fibrillation episodes being classified as persistent (OR 2.33 (1.13-4.80)) were significant predictors for non-response to vernakalant. Electrical cardioversion was successful in all patients but one within 196 min (IQR 149-300) of administration of first dosage of vernakalant. No serious adverse events could be observed. 3 patients needed further in-patient care.ConclusionManagement of recent-onset atrial fibrillation consisting of intravenous vernakalant followed by electrical cardioversion in case of failure appears safe and efficacious. Achieving a rapid conversion, this approach could potentially save resources and costs.

| S-EPMC6626112 | biostudies-literature

Electrical Guidance of Human Stem Cells in the Rat Brain.

Project description:Limited migration of neural stem cells in adult brain is a roadblock for the use of stem cell therapies to treat brain diseases and injuries. Here, we report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. We developed a safe stimulation paradigm to deliver directional currents in the brain. Tracking cells expressing GFP demonstrated electrical mobilization and guidance of migration of human neural stem cells, even against co-existing intrinsic cues in the rostral migration stream. Transplanted cells were observed at 3 weeks and 4 months after stimulation in areas guided by the stimulation currents, and with indications of differentiation. Electrical stimulation thus may provide a potential approach to facilitate brain stem cell therapies.

| S-EPMC5511115 | biostudies-literature

Multi-channel transorbital electrical stimulation for effective stimulation of posterior retina.

Project description:Transorbital electrical stimulation (tES) has been studied as a new noninvasive method for treating intractable eye diseases by delivering weak electrical current to the eye through a pair of electrodes attached to the skin around the eye. Studies have reported that the therapeutic effect of tES is determined by the effective stimulation of retinal cells that are densely distributed in the posterior part of the retina. However, in conventional tES with a pair of electrodes, a greater portion of the electric field is delivered to the anterior part of the retina. In this study, to address this issue, a new electrode montage with multiple electrodes was proposed for the effective delivery of electric fields to the posterior retina. Electric field analysis based on the finite element method was performed with a realistic human head model, and optimal injection currents were determined using constrained convex optimization. The resultant electric field distributions showed that the proposed multi-channel tES enables a more effective stimulation of the posterior retina than the conventional tES with a pair of electrodes.

| S-EPMC8105361 | biostudies-literature

Optimization of electrical stimulation parameters for cardiac tissue engineering.

Project description:In vitro application of pulsatile electrical stimulation to neonatal rat cardiomyocytes cultured on polymer scaffolds has been shown to improve the functional assembly of cells into contractile engineered cardiac tissues. However, to date, the conditions of electrical stimulation have not been optimized. We have systematically varied the electrode material, amplitude and frequency of stimulation to determine the conditions that are optimal for cardiac tissue engineering. Carbon electrodes, exhibiting the highest charge-injection capacity and producing cardiac tissues with the best structural and contractile properties, were thus used in tissue engineering studies. Engineered cardiac tissues stimulated at 3 V/cm amplitude and 3 Hz frequency had the highest tissue density, the highest concentrations of cardiac troponin-I and connexin-43 and the best-developed contractile behaviour. These findings contribute to defining bioreactor design specifications and electrical stimulation regime for cardiac tissue engineering.

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Mapping effective connectivity in the human brain with concurrent intracranial electrical stimulation and BOLD-fMRI.

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| S-EPMC5534177 | biostudies-literature

Brief Electrical Stimulation Triggers an Effective Regeneration of Leech CNS.

Project description:The search for therapeutic strategies to promote neuronal regeneration following injuries toward functional recovery is of great importance. Brief low-frequency electrical stimulation (ES) has been reported as a useful method to improve neuronal regeneration in different animal models; however, the effect of ES on single neuron behavior has not been shown. Here, we study the effect of brief ES on neuronal regeneration of the CNS of adult medicinal leeches. Studying the regeneration of selected sets of identified neurons allow us to quantify the ES effect per cell type at the single-cell level. Chains of the CNS that were subjected to cut injury were observed for 3?d, and the spontaneous regeneration was compared with the electrically stimulated injured chains. We show that the ES improves the efficiency of regeneration of Retzius cells, as larger masses of the total branching tree traverse the injury site with better directed growth with no effect on the average branching tree length. No antero-posterior polarity was found along regeneration within the leech CNS. Moreover, the microglial cell distribution was examined revealing more microglial cells in proximity to the stimulation site compared with non-stimulated. Our results lay a foundation for future ES-based neuroregenerative therapies.

| S-EPMC7317182 | biostudies-literature

Human primary myotubes +/- electrical pulse stimulation

Project description:Human myogenic progenitor cells (MPCs) were isolated from the gracilis of two patients (1 female and 1 male) undergoing anterior cruciate ligament reconstruction (age 30-34 years) using a human anti-CD56 (1:20, Cat# 355503, Biolegend) antibody for FACS. Cells were passaged 2-3 times in growth media consisting of Ham’s F-10 (Thermofisher), 20% fetal bovine serum (FBS, Atlanta Biological, Minneapolis, MN, USA), 1% penicillin/streptomycin and 10ng/ml basic fibroblast growth-factor (bFGF, Peprotech, Rocky Hill, NJ, USA). Cells were differentiated into myotubes for 5 days using MyoCult differentiation media (Stemcell Technologies, Vancouver, Canada). On the fifth day, fresh media was added just prior to electrical pulse stimulation (E). Cells were then either stimulated at 12 V, 1 Hz, 2 ms for 24 hr (IonOptix C‐Pace EP, Westwood, MA, USA) or had electrodes placed in wells with no stimulation (E(+) or E(-)), followed by immediate RNA extraction using Qiazol (Qiagen, Hilden, Germany).

2021-08-20 | E-MTAB-10833 | biostudies-arrayexpress

Highly efficient modeling and optimization of neural fiber responses to electrical stimulation.

Project description:Peripheral neuromodulation has emerged as a powerful modality for controlling physiological functions and treating a variety of medical conditions including chronic pain and organ dysfunction. The underlying complexity of the nonlinear responses to electrical stimulation make it challenging to design precise and effective neuromodulation protocols. Computational models have thus become indispensable in advancing our understanding and control of neural responses to electrical stimulation. However, existing approaches suffer from computational bottlenecks, rendering them unsuitable for real-time applications, large-scale parameter sweeps, or sophisticated optimization. In this work, we introduce an approach for massively parallel estimation and optimization of neural fiber responses to electrical stimulation using machine learning techniques. By leveraging advances in high-performance computing and parallel programming, we present a surrogate fiber model that generates spatiotemporal responses to a wide variety of cuff-based electrical peripheral nerve stimulation protocols. We used our surrogate fiber model to design stimulation parameters for selective stimulation of pig and human vagus nerves. Our approach yields a several-orders-of-magnitude improvement in computational efficiency while retaining generality and high predictive accuracy, demonstrating its robustness and potential to enhance the design and optimization of peripheral neuromodulation therapies.

| S-EPMC11365978 | biostudies-literature

Transcranial electrical stimulation accelerates human sleep homeostasis.

Project description:The sleeping brain exhibits characteristic slow-wave activity which decays over the course of the night. This decay is thought to result from homeostatic synaptic downscaling. Transcranial electrical stimulation can entrain slow-wave oscillations (SWO) in the human electro-encephalogram (EEG). A computational model of the underlying mechanism predicts that firing rates are predominantly increased during stimulation. Assuming that synaptic homeostasis is driven by average firing rates, we expected an acceleration of synaptic downscaling during stimulation, which is compensated by a reduced drive after stimulation. We show that 25 minutes of transcranial electrical stimulation, as predicted, reduced the decay of SWO in the remainder of the night. Anatomically accurate simulations of the field intensities on human cortex precisely matched the effect size in different EEG electrodes. Together these results suggest a mechanistic link between electrical stimulation and accelerated synaptic homeostasis in human sleep.

| S-EPMC3573006 | biostudies-literature

Quantitative LC-MSMS of human muscle cells after electrical pulse stimulation

Project description:We hypothesized that muscle contraction produces a cellular stress signal capable to increase lipolysis to sustain fuel availability during exercise. The aim of the present study was to identify novel exercise-regulated myokines, aka exerkines, able to promote lipolysis in human adipocytes. To this end, human primary myotubes from lean healthy volunteers were submitted to electrical pulse stimulation to mimic either acute intense or chronic moderate exercise. Conditioned media experiments with hMADS adipocytes were performed. Unbiased proteomic and ELISA analyses were applied in conditioned media and human plasma samples. Real-time qPCR was performed in cultured myotubes and muscle biopsy samples.

2020-05-26 | PXD014126 | Pride

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