Effects of electrical fields on cardiomyocyte differentiation of embryonic stem cells

Sauer, Heinrich; Rahimi, Gohar; Hescheler, Jürgen; Wartenberg, Maria

doi:10.1002/(sici)1097-4644(19991215)75:4<710::aid-jcb16>3.0.co;2-z

Cited by 202 publications

(153 citation statements)

References 44 publications

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“…A new study by Ventura et al [2005] has demonstrated the ability of 0.8 mT (rms) 50 Hz magnetic fields to influence stem cell differentiation, increasing the number of cells that become myocardial cells. Using electric field stimulation Sauer et al [1999] increased stem cell differentiation into cardiomyocytes via a reactive oxygen species mechanism.…”

Section: Repairing the Damagementioning

confidence: 99%

The influence of extremely low frequency magnetic fields on cytoprotection and repair

Robertson

Thomas

Bureau

et al. 2006

Bioelectromagnetics

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Ischemia-reperfusion injuries, such as those suffered from various types of cardiovascular disease, are major causes of death and disability. For relatively short periods of ischemia, much of the damage is potentially reversible and in fact, does not occur until the influx of oxygen during the reperfusion stage. Because of this, there is a window of opportunity to protect the ischemic tissue. Here, we review several mechanisms of protection, such as heat shock proteins, opioids, collateral blood flow, and nitric oxide induction, and the evidence indicating that magnetic fields may be used as a means of providing protection via each of these mechanisms. While there are few studies demonstrating direct protection with magnetic field therapies, there are a number of published reports indicating that electromagnetic fields may be able to influence some of the biochemical systems with protective applications.

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Section: Repairing the Damagementioning

confidence: 99%

The influence of extremely low frequency magnetic fields on cytoprotection and repair

Robertson

Thomas

Bureau

et al. 2006

Bioelectromagnetics

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“…Previous reports have shown a link between ROS and cardiac differentiation. Indeed, electric field stimulation of EB increases the amount of cardiomyocytes through the augmentation of intracellular ROS and the nuclear translocation of NF-B (Sauer et al, 1999). Other pathways linking ROS to cardiac development include PI3-kinase as its inhibition impairs ROS production and, as a consequence, cardiac differentiation (Sauer et al, 2000).…”

mentioning

confidence: 99%

“…After 2 d, EBs were collected and cultured in suspension for 2 d. At day 4 medium was changed and the following day (day 5), EBs were plated to gelatin-coated 24-well plates or glass coverslips (Meyer et al, 2000). At day 8 of differentiation, EBs containing 2 or more beating foci were considered beating EBs (Sauer et al, 1999;Meyer et al, 2000;Li et al, 2002). This scoring technique is based on the fact that an EB containing only a single beating cluster is usually very small and not representative of a typical beating EB in which several beating clusters are usually visible.…”

mentioning

confidence: 99%

The NADPH Oxidase NOX4 Drives Cardiac Differentiation: Role in Regulating Cardiac Transcription Factors and MAP Kinase Activation

Li¹,

Stouffs²,

Serrander³

et al. 2006

MBoC

262

203

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Reactive oxygen species (ROS) generated by the NOX family of NADPH oxidases have been described to act as second messengers regulating cell growth and differentiation. However, such a function has hitherto not been convincingly demonstrated. We investigated the role of NOX-derived ROS in cardiac differentiation using mouse embryonic stem cells. ROS scavengers prevented the appearance of spontaneously beating cardiac cells within embryoid bodies. Downregulation of NOX4, the major NOX isoform present during early stages of differentiation, suppressed cardiogenesis. This was rescued by a pulse of low concentrations of hydrogen peroxide 4 d before spontaneous beating appears. Mechanisms of ROS-dependent signaling included p38 mitogen-activated protein kinase (MAPK) activation and nuclear translocation of the cardiac transcription factor myocyte enhancer factor 2C (MEF2C). Our results provide first molecular evidence that the NOX family of NADPH oxidases regulate vertebrate developmental processes. INTRODUCTIONReactive oxygen species (ROS) are generated either in a nonregulated manner as side products of several enzymatic systems (e.g., cyclooxygenases, nitric oxide [NO] synthases, mitochondrial cytochromes) or in a regulated way as main products of superoxide producing enzymes, the NADPH oxidases. In the mouse, the family of NADPH oxidases includes NOX1, NOX2 (gp91 phox ), NOX3, and NOX4.Excessive cellular generation of ROS, such as superoxide anions (O 2 Ϫ ) and hydrogen peroxide (H 2 O 2 ), is potentially destructive and is used by phagocytes to kill invading microorganisms. Under normal conditions, scavenging mechanisms (e.g., superoxide dismutase, catalase, glutathioneglutathione peroxidase system) remove excessive amounts of ROS. Under stress conditions, however, the production of ROS may exceed the reducing capacity of the cell and damage cellular functions. Small amounts of ROS, on the other hand, can function as intracellular second messengers and activate signaling cascades involved in growth and differentiation of many cell types (for review see Rhee, 1999;Laloi et al., 2004). For example, the MAP kinase-signaling pathway is sensitive to ROS (Torres and Forman, 2003). Moreover, distinct signaling pathways have differential sensitivity to oxidative stress, leading to dose-dependent effect on, for example, cardiomyocytes on which ROS can induce hypertrophy or apoptosis (Kwon et al., 2003). Transcription factors such as NF-B, p53, and AP-1 are redox-sensitive and can be directly modified by ROS, providing a link with the control of gene expression (Morel and Barouki, 1999).Cardiac differentiation can be studied by differentiating mouse embryonic stem cells (ESC) into embryoid bodies (EB), where the appearance of spontaneously beating cardiomyocytes is observed after 7-8 d of culture. This system thus provides a unique experimental model to study the role of ROS and ROS-generating enzymes in the regulation of cardiomyocyte growth and differentiation in vitro. Previous reports have shown a link between ROS and...

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“…High amounts of ROS can cause cell death and disrupt or inhibit gene expression but at lower levels ROS can increase the proliferation and differentiation by activating many signaling cascades and transcription factors 18,[37][38][39] . However, the actual effect of ROS in this stimulation setup still needs to be investigated.…”

Section: Discussionmentioning

confidence: 99%

The Combination of Electric Current and Copper Promotes Neuronal Differentiation of Adipose-Derived Stem Cells

Jaatinen

Salemi

Miettinen³

et al. 2014

Ann Biomed Eng

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Damage to the nervous system can be caused by several types of insults, and it always has a great effect on the life of an individual. Due to the limited availability of neural transplants, alternative approaches for neural regeneration must be developed. Stem cells have a great potential to support neuronal regeneration. Human adipose-derived stem cells (hADSCs) have gained increasing interest in the fields of regenerative medicine due to their multilineage potential and easy harvest compared to other stem cells. In this study, we present a growth factor-free method for the differentiation of hADSCs toward neuron-like cells. We investigated the effect of electric current and copper on neuronal differentiation. We analyzed the morphological changes, the mRNA and protein expression levels in the stimulated cells and showed that the combination of current and copper induces stem cell differentiation toward the neuronal lineage with elongation of the cells and the upregulation of neuron-specific genes and proteins. The induction of the neuronal differentiation of hADSCs by electric field and copper may offer a novel approach for stem cell differentiation and may be a useful tool for safe stem cell-based therapeutic applications. Abstract and key termsDamage to the nervous system can be caused by several types of insults, and it always has a great effect on the life of an individual. Due to the limited availability of neural transplants, alternative approaches for neural regeneration must be developed. Stem cells have a great potential to support neuronal regeneration.Human adipose-derived stem cells (hADSCs) have gained increasing interest in the fields of regenerative medicine due to their multilineage potential and easy harvest compared to other stem cells. In this study, we present a growth factor-free method for the differentiation of hADSCs toward neuron-like cells. We investigated the effect of electric current and copper on neuronal differentiation. We analyzed the morphological changes, the mRNA and protein expression levels in the stimulated cells and showed that the combination of current and copper induces stem cell differentiation toward the neuronal lineage with elongation of the cells and the upregulation of neuron-specific genes and proteins. The induction of the neuronal differentiation of hADSCs by electric field and copper may offer a novel approach for stem cell differentiation and may be a useful tool for safe stem cell-based therapeutic applications.

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Effects of electrical fields on cardiomyocyte differentiation of embryonic stem cells

Cited by 202 publications

References 44 publications

The influence of extremely low frequency magnetic fields on cytoprotection and repair

The influence of extremely low frequency magnetic fields on cytoprotection and repair

The NADPH Oxidase NOX4 Drives Cardiac Differentiation: Role in Regulating Cardiac Transcription Factors and MAP Kinase Activation

The Combination of Electric Current and Copper Promotes Neuronal Differentiation of Adipose-Derived Stem Cells

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