Electrical stimulation of cell growth and neurogenesis using conductive and nonconductive microfibrous scaffolds

2019 ◽  
Vol 11 (6) ◽  
pp. 264-279
Author(s):  
Simon Grossemy ◽  
Peggy P Y Chan ◽  
Pauline M Doran

Abstract The effect of exogenous electrical stimulation on cell viability, attachment, growth, and neurogenesis was examined using PC12 cells in microfibrous viscose-rayon scaffolds immersed in culture medium. The scaffolds were applied either in their nonconductive state or after coating the fibres with 200 nm of gold to give a scaffold sheet resistivity of (13 ± 1.3) Ω square−1. The cells were treated for 12 days using direct current electrical stimulation of 2 h per day. No cytotoxic effects were observed when up to 500 mV (8.3 mV mm−1) was applied to the scaffolds without gold, or when up to 100 mV (1.7 mV mm−1) was applied to the scaffolds with gold. Compared with unstimulated cells, whereas electrical stimulation significantly enhanced cell growth and attachment in the nonconductive scaffolds without gold, similar effects were not found for the conductive scaffolds with gold. Neural differentiation in the presence of nerve growth factor was improved by electrical stimulation in both scaffolds; however, neurite development and the expression of key differentiation markers were greater in the nonconductive scaffolds without gold than in the scaffolds with gold. Application of the same current to scaffolds with and without gold led to much higher levels of neurogenesis in the scaffolds without gold. This work demonstrates that substantial benefits in terms of cell growth and neural differentiation can be obtained using electric fields exerted across nonconductive microfibrous scaffolds, and that this approach to electrical stimulation can be more effective than when the stimulus is applied to cells on conductive scaffolds.

2021 ◽  
Vol 22 (1) ◽  
pp. 394
Author(s):  
Simone Krueger ◽  
Alexander Riess ◽  
Anika Jonitz-Heincke ◽  
Alina Weizel ◽  
Anika Seyfarth ◽  
...  

In cell-based therapies for cartilage lesions, the main problem is still the formation of fibrous cartilage, caused by underlying de-differentiation processes ex vivo. Biophysical stimulation is a promising approach to optimize cell-based procedures and to adapt them more closely to physiological conditions. The occurrence of mechano-electrical transduction phenomena within cartilage tissue is physiological and based on streaming and diffusion potentials. The application of exogenous electric fields can be used to mimic endogenous fields and, thus, support the differentiation of chondrocytes in vitro. For this purpose, we have developed a new device for electrical stimulation of chondrocytes, which operates on the basis of capacitive coupling of alternating electric fields. The reusable and sterilizable stimulation device allows the simultaneous use of 12 cavities with independently applicable fields using only one main supply. The first parameter settings for the stimulation of human non-degenerative chondrocytes, seeded on collagen type I elastin-based scaffolds, were derived from numerical electric field simulations. Our first results suggest that applied alternating electric fields induce chondrogenic re-differentiation at the gene and especially at the protein level of human de-differentiated chondrocytes in a frequency-dependent manner. In future studies, further parameter optimizations will be performed to improve the differentiation capacity of human cartilage cells.


Blood ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 331-339 ◽  
Author(s):  
J.L. Vaerman ◽  
P. Moureau ◽  
F. Deldime ◽  
P. Lewalle ◽  
C. Lammineur ◽  
...  

Antisense oligodeoxyribonucleotides (ODNs) are now being extensively investigated in an attempt to achieve cell growth suppression through specific targeting of genes related to cell proliferation, despite increasing evidence of non-antisense cytotoxic effects. In the context of anti-BCR/ABL antisense strategies in chronic myeloid leukemia, we have re-examined the antiproliferative effect of phosphodiester and phosphorothioate ODNs on the leukemic cell line BV173 and on CD34+ bone marrow cells in liquid culture. The 3′ sequences of the ODNs determine their effect. At concentrations of 10 μmol/L (for phosphorothioate ODNs) or 25 μmol/L (for phosphodiester ODNs), all the tested ODNs exert an antiproliferative activity, except those that contain a cytosine residue at either their two most terminal 3′ positions. We show that this antiproliferative effect is due to the toxicity of the d-NMPs (5′ monophosphate deoxyribonucleosides), the enzymatic hydrolysis products of the ODNs in culture medium. The toxicity of the d-NMPs on hematologic cells depends on their nature (d-CMP [2′deoxycytidine 5′-monophosphate] is not cytotoxic), on their concentration (d-GMP [2′-deoxyguanosine 5′-monophosphate], TMP [thymidine 5′-monophosphate], and d-AMP [2′-deoxyadenosine 5′-monophosphate] are cytotoxic at concentrations between 5 and 10 μmol/L), and on the coincident presence of other d-NMPs in the culture medium (d-CMP neutralizes the toxicity of d-AMP, d-GMP, or TMP). The antiproliferative activity of ODNs is thus restricted to conditions where the 3′ hydrolysis process by exonucleases generates significant amounts of d-NMPs with a low proportion of d-CMP. Our results reveal a novel example of a nonantisense effect of ODNs, which should be taken into account when performing any experiment using assumed antisense ODNs.


2020 ◽  
Vol 14 (1) ◽  
pp. 6-18
Author(s):  
Juan Jairo Vaca González ◽  
Juan Felipe Escobar Huertas ◽  
Diego Alexander Garzón Alvarado

Electrical stimulation is a non-invasive therapy used to stimulate chondrocyte dynamics: proliferation, migration, morphology and molecular synthesis. Some studies have evidenced the role of frequency in the generation of electric fields; however, the electrical stimulation sensed by chondrocytes when the frequency varies is not well-documented. Accordingly, a computational model was implemented to assess the frequency dependence of electric fields that stimulate chondrocytes. Cells were modelled in three different scenarios: monolayer cultures, cartilage explants and scaffolds. Chondrocytes were stimulated with 100 Vp-p at frequencies of 0.001, 1, 10, 50, 100 and 1000 kHz. Results showed that frequency is a relevant factor when considering the stimulation of biological samples, since electric fields increased as frequencies were higher. Moreover, chondrocytes experienced different electric fields in both cytoplasm and extracellular environment. This model provides relevant information about the electrical parameters to stimulate cells; in fact, it could enhance experimental procedures, predicting the stimulation that improves chondrocyte dynamics. Electric fields are a promising tool to maintain either well-structured chondrocytes or biomimetic materials used in regenerative therapies such as autologous implantation to treat hyaline cartilage injuries.


2019 ◽  
Author(s):  
P. Yu. Privalova ◽  
A. Yu. Gerasimenko ◽  
V. A. Petukhov ◽  
E. N. Shimarov ◽  
I. A. Suyetina ◽  
...  

2019 ◽  
Vol 55 (66) ◽  
pp. 9833-9836 ◽  
Author(s):  
Hanjun Sun ◽  
Dongqin Yu ◽  
Yijia Guan ◽  
Zhi Du ◽  
Jinsong Ren ◽  
...  

A new photoelectrochemical approach which could generate an interfacial electric field, release ions and induce reactive oxygen species (ROS) in PC12 cells under NIR irradiation, realizing wireless neurite development and outgrowth, was put forward.


1979 ◽  
Vol 178 (2) ◽  
pp. 391-395 ◽  
Author(s):  
Maureen A. L. Melvin ◽  
Hamish M. Keir

Cultures of BHK-21/C13 cells, whose growth was inhibited by deprivation of serum, were stimulated to grow by addition of serum to the culture medium. Addition of MgCl2 to the medium, to increase the concentration of Mg2+ ions by 15mm, 30min before addition of serum, had no effect on the stimulation of cell growth, but inhibited the accumulation of cellular spermidine, so that the spermidine/spermine molar ratio was lower in these cultures than in cultures that had received no additional cations. The increase in the activity of ornithine decarboxylase that occurs 4–5h after serum ‘step-up’ was substantially diminished by increasing the concentration of Mg2+ ions, but not of Na+ or K+ ions, in the medium by 30mm, 30min before addition of serum, and this inhibition was maintained for at least 24h. Methylglyoxal bis(guanylhydrazone), added to serum-deprived cultures to a concentration of 20μm, 30min before addition of serum, severely inhibited the increase in cell growth. The inhibitory effects of the drug were prevented by simultaneous addition of spermidine to the medium (to 100μm), and were partly prevented by the simultaneous addition of Mg2+ ions (to 30mm). Mg2+ ions were particularly effective in overcoming the inhibitory effect of methylglyoxal bis(guanylhydrazone) on the synthesis of DNA. Thus although a certain lack of specificity for cations exists in BHK-21/C13 cells, in that Mg2+ ions can be substituted for polyamines, particularly spermidine, to some extent, there are cellular processes for which the requirement for polyamines as cations is specific.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sangjun Lee ◽  
Jimin Park ◽  
Jinuk Kwon ◽  
Dong Hwan Kim ◽  
Chang-Hwan Im

AbstractTransorbital 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.


Blood ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 331-339 ◽  
Author(s):  
J.L. Vaerman ◽  
P. Moureau ◽  
F. Deldime ◽  
P. Lewalle ◽  
C. Lammineur ◽  
...  

Abstract Antisense oligodeoxyribonucleotides (ODNs) are now being extensively investigated in an attempt to achieve cell growth suppression through specific targeting of genes related to cell proliferation, despite increasing evidence of non-antisense cytotoxic effects. In the context of anti-BCR/ABL antisense strategies in chronic myeloid leukemia, we have re-examined the antiproliferative effect of phosphodiester and phosphorothioate ODNs on the leukemic cell line BV173 and on CD34+ bone marrow cells in liquid culture. The 3′ sequences of the ODNs determine their effect. At concentrations of 10 μmol/L (for phosphorothioate ODNs) or 25 μmol/L (for phosphodiester ODNs), all the tested ODNs exert an antiproliferative activity, except those that contain a cytosine residue at either their two most terminal 3′ positions. We show that this antiproliferative effect is due to the toxicity of the d-NMPs (5′ monophosphate deoxyribonucleosides), the enzymatic hydrolysis products of the ODNs in culture medium. The toxicity of the d-NMPs on hematologic cells depends on their nature (d-CMP [2′deoxycytidine 5′-monophosphate] is not cytotoxic), on their concentration (d-GMP [2′-deoxyguanosine 5′-monophosphate], TMP [thymidine 5′-monophosphate], and d-AMP [2′-deoxyadenosine 5′-monophosphate] are cytotoxic at concentrations between 5 and 10 μmol/L), and on the coincident presence of other d-NMPs in the culture medium (d-CMP neutralizes the toxicity of d-AMP, d-GMP, or TMP). The antiproliferative activity of ODNs is thus restricted to conditions where the 3′ hydrolysis process by exonucleases generates significant amounts of d-NMPs with a low proportion of d-CMP. Our results reveal a novel example of a nonantisense effect of ODNs, which should be taken into account when performing any experiment using assumed antisense ODNs.


Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 352
Author(s):  
Oriol Careta ◽  
Jordina Fornell ◽  
Eva Pellicer ◽  
Elena Ibañez ◽  
Andreu Blanquer ◽  
...  

A Ti-based alloy (Ti45Zr15Pd30Si5Nb5) with already proven excellent mechanical and biocompatibility features has been coated with piezoelectric zinc oxide (ZnO) to induce the electrical self-stimulation of cells. ZnO was grown onto the pristine alloy in two different morphologies: a flat dense film and an array of nanosheets. The effect of the combined material on osteoblasts (electrically stimulable cells) was analyzed in terms of proliferation, cell adhesion, expression of differentiation markers and induction of calcium transients. Although both ZnO structures were biocompatible and did not induce inflammatory response, only the array of ZnO nanosheets was able to induce calcium transients, which improved the proliferation of Saos-2 cells and enhanced the expression of some early differentiation expression genes. The usual motion of the cells imposes strain to the ZnO nanosheets, which, in turn, create local electric fields owing to their piezoelectric character. These electric fields cause the opening of calcium voltage gates and boost cell proliferation and early differentiation. Thus, the modification of the Ti45Zr15Pd30Si5Nb5 surface with an array of ZnO nanosheets endows the alloy with smart characteristics, making it capable of electric self-stimulation.


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