Unraveling the mechanistic effects of electric field stimulation towards directing stem cell fate and function: A tissue engineering perspective

Abstract

Electric field (EF) stimulation can play a vital role in eliciting appropriate stem cell response. Such an approach is recently being established to guide stem cell differentiation through osteogenesis/neurogenesis/cardiomyogenesis. Despite significant recent efforts, the biophysical mechanisms by which stem cells sense, interpret and transform electrical cues into biochemical and biological signals still remain unclear. The present review critically analyses the variety of EF stimulation approaches that can be employed to evoke appropriate stem cell response and also makes an attempt to summarize the underlying concepts of this notion, placing special emphasis on stem cell based tissue engineering and regenerative medicine. This review also discusses the major signaling pathways and cellular responses that are elicited by electric stimulation, including the participation of reactive oxygen species and heat shock proteins, modulation of intracellular calcium ion concentration, ATP production and numerous other events involving the clustering or reassembling of cell surface receptors, cytoskeletal remodeling and so on. The specific advantages of using external electric stimulation in different modalities to regulate stem cell fate processes are highlighted with explicit examples, in vitro and in vivo.
http://www.sciencedirect.com/science/article/pii/S0142961217306300

The use of electric, magnetic, and electromagnetic field for directed cell migration and adhesion in regenerative medicine

Directed cell migration and adhesion is essential to embryonic development, tissue formation and wound healing. For decades it has been reported that electric field (EF), magnetic field (MF) and electromagnetic field (EMF) can play important roles in determining cell differentiation, migration, adhesion, and even wound healing. Combinations of these techniques have revealed new and exciting explanations for how cells move and adhere to surfaces; how the migration of multiple cells are coordinated and regulated; how cells interact with neighboring cells, and also to changes in their microenvironment. In some cells, speed and direction are voltage dependent. Data suggests that the use of EF, MF and EMF could advance techniques in regenerative medicine, tissue engineering and wound healing.
http://onlinelibrary.wiley.com/doi/10.1002/btpr.2371/full

Low Frequency Magnetic Fields Induce Autophagy-associated Cell Death in Lung Cancer through miR-486-mediated Inhibition of Akt/mTOR Signaling Pathway

Low frequency magnetic fields (LF-MFs) can affect cell proliferation in a cell-type and intensity-dependent way. Previous study has reported the anti-tumor effect of LF-MFs in lung cancers. Our previous study also optimized the intensity and duration of LF-MFs to effectively inhibit the proliferation of lung cancer cells. However, the anti-tumor mechanism of LF-MFs remains unclear, which limit the clinical application of LF-MFs in anti-tumor therapy. Here, in a well-established Lewis Lung Cancer (LLC) mouse model, we found that LF-MFs inhibit tumor growth and induce an autophagic cell death in lung cancer. We also found that LF-MFs could up-regulate the expression level of miR-486, which was involved in LF-MFs activated cell autophagy. Furthermore, we found B-cell adaptor for phosphatidylinositol 3-kinase (BCAP) is a direct target of miR-486. miR-486 inhibit AKT/mTOR signaling through inhibiting expression of BCAP. Moreover, a decreased expression of miR-486 and an increased expression of BCAP were found in tumor tissues of lung cancer patients. Taken together, this study proved that LF-MFs can inhibit lung cancers through miR-486 induced autophagic cell death, which suggest a clinical application of LF-MFs in cancer treatment.
https://www.nature.com/articles/s41598-017-10407-w

Magnetic Fields and Reactive Oxygen Species

Abstract

Reactive oxygen species (ROS) ubiquitously exist in mammalian cells to participate in various cellular signaling pathways. The intracellular ROS levels are dependent on the dynamic balance between ROS generation and elimination. In this review, we summarize reported studies about the influences of magnetic fields (MFs) on ROS levels. Although in most cases, MFs increased ROS levels in human, mouse, rat cells, and tissues, there are also studies showing that ROS levels were decreased or not affected by MFs. Multiple factors could cause these discrepancies, including but not limited to MF type/intensity/frequency, exposure time and assay time-point, as well as different biological samples examined. It will be necessary to investigate the influences of different MFs on ROS in various biological samples systematically and mechanistically, which will be helpful for people to get a more complete understanding about MF-induced biological effects. In addition, reviewing the roles of MFs in ROS modulation may open up new scenarios of MF application, which could be further and more widely adopted into clinical applications, particularly in diseases that ROS have documented pathophysiological roles
http://www.mdpi.com/1422-0067/18/10/2175

Enhancing cold atmospheric plasma treatment of cancer cells by static magnetic field

Abstract

It has been reported since late 1970 that magnetic field interacts strongly with biological systems. Cold atmospheric plasma (CAP) has also been widely studied over the past few decades in physics, biology, and medicine. In this study, we propose a novel idea to combine static magnetic field (SMF) with CAP as a tool for cancer therapy. Breast cancer cells and wild type fibroblasts were cultured in 96-well plates and treated by CAP with or without SMF. Breast cancer cells MDA-MB-231 showed a significant decrease in viability after direct plasma treatment with SMF (compared to only plasma treatment). In addition, cancer cells treated by the CAP-SMF-activated medium (indirect treatment) also showed viability decrease but was slightly weaker than the direct plasma-SMF treatment. By integrating the use of SMF and CAP, we were able to discover their advantages that have yet to be utilized. Bioelectromagnetics. 38:53–62, 2017. © 2016 Wiley Periodicals, Inc.

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INTRODUCTION

In the past few decades, cold atmospheric plasma (CAP) has been widely used in various fields such as material processing [Zelzer et al., 2012], bacterial inactivation [Deng et al., 2007], wound healing, cut coagulation [Isbary et al., 2012], cancer therapy [Shashurin et al., 2008; Keidar et al., 2011; Barekzi and Laroussi, 2012; Walk et al., 2013], and viral destruction [Shi et al., 2012]. The temperature of heavy species in CAP is usually close to room temperature, allowing its application to living tissue treatment [Keidar, 2015].
It has been reported since the late 1970s that a magnetic field (MF) appears to have a strong effect on biological systems [Bawin and Sabbot, 1978; Liboff, 1985; Halle, 1988; Liboff and McLeod, 1988]. Research on the electromagnetic field effect on biological systems advanced after Wertheimer and Leeper [1979] found that the likelihood of developing leukemia in children increased as they were present in 60 Hz frequency electromagnetic field. As the research progressed, it appeared as though vibrational energy levels in the ion–protein complex were pumping into the system, which was creating parametric resonance. This occurs when the atoms shake slightly [Lednev, 1991]. This “shaking” is an anomaly that can change ion flux through the cell membrane [Liboff et al., 1987] or cell mobility [McLeod et al., 1987; Smith et al., 1987]. Santoro et al. [1997] showed that extremely low frequency (ELF) MFs influence physiological processes in different organisms, such as plasma membrane structure modification and initiation of signal cascade pathways interference. Cell membrane morphology modification by ELF was again reaffirmed by Ikehara et al. [2003], who found that exposure to the ELF MF has reversible effects on NH inplane bending and CN stretching vibrations of peptide linkages, and changes the secondary structures of α-helix and β-sheet in cell membrane proteins.
Link to Publication

Quantum Information Medicine: Bit as It—The Future Direction of Medical Science: Antimicrobial and Other Potential Nontoxic Treatments

Experimental evidence has accumulated to suggest that biologically efficacious informational effects can be derived mimicking active compounds solely through electromagnetic distribution upon aqueous systems affecting biological systems. Empirically rigorous demonstrations of anti-microbial agent associated electromagnetic informational inhibition of MRSA, Entamoeba histolytica, Trichomonas vaginalis, Candida albicans and a host of other important and various reported effects have been evidenced, such as the electro-informational transfer of retinoic acid influencing human neuroblastoma cells and stem teratocarcinoma cells. Cell proliferation and differentiation effects from informationally affected fields interactive with aqueous systems are measured via microscopy, statistical analysis, reverse transcription polymerase chain reaction and other techniques. Information associated with chemical compounds affects biological aqueous systems, sans direct systemic exposure to the source molecule. This is a quantum effect, based on the interactivity between electromagnetic fields, and aqueous ordered coherence domains. The encoding of aqueous systems and tissue by photonic transfer and instantiation of information rather than via direct exposure to potentially toxic drugs and physical substances holds clear promise of creating inexpensive non-toxic medical treatments.
https://www.researchgate.net/publication/305343138_Quantum_Information_Medicine_Bit_as_It-The_Future_Direction_of_Medical_Science_Antimicrobial_and_Other_Potential_Nontoxic_Treatments

Power frequency magnetic field promotes a more malignant phenotype in neuroblastoma cells via redox-related mechanisms

In accordance with the classification of the International Agency for Research on Cancer, extremely low frequency magnetic fields (ELF-MF) are suspected to promote malignant progression by providing survival advantage to cancer cells through the activation of critical cytoprotective pathways. Among these, the major antioxidative and detoxification defence systems might be targeted by ELF-MF by conferring cells significant resistance against clinically-relevant cytotoxic agents. We investigated whether the hyperproliferation that is induced in SH-SY5Y human neuroblastoma cells by a 50 Hz, 1 mT ELF magnetic field was supported by improved defence towards reactive oxygen species (ROS) and xenobiotics, as well as by reduced vulnerability against both H 2 O 2 and anti-tumor ROS-generating drug doxorubicin. ELF-MF induced a proliferative and survival advantage by activating key redox-responsive antioxidative and detoxification cytoprotective pathways that are associated with a more aggressive behavior of neuroblastoma cells. This was coupled with the upregulation of the major sirtuins, as well as with increased signaling activity of the erythroid 2-related nuclear transcription factor 2 (NRF2). Interestingly, we also showed that the exposure to 50 Hz MF as low as 100 µT may still be able to alter behavior and responses of cancer cells to clinically-relevant drugs.
https://www.researchgate.net/publication/319678929_Power_frequency_magnetic_field_promotes_a_more_malignant_phenotype_in_neuroblastoma_cells_via_redox-related_mechanisms