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Stem cells are undifferentiated cells capable of self-renewal and differentiation into various specialized cell type. their unique properties make them invaluable for repairing damaged tissues and organ, offering hopes for treating degenerative diseases and currently lack effective therapies. Recent advancements have shown that electrical impulses play a pivotal rule in influencing the behavior and differentiation of stem cells, offering new insights into their manipulation and differentiation. Graphen as a single layer of carbon atoms has shown potentials in stimulating stem cell which will be further discussed in this article.
Direct Current (DC) Stimulation
Setup: Involves placing electrodes in the vicinity of the stem cells or within a culture medium.
Effect: DC stimulation affects the electrical potential across the cell membrane, which can influence ion transport, cell signaling pathways, and gene expression.
Applications: Used to promote stem cell differentiation into specific lineages (e.g., neurons, muscle cells) or enhance their proliferation.
Alternating Current (AC) Stimulation
Setup: Similar to DC stimulation but involves oscillating electrical fields.
Effect: AC stimulation can modulate cellular activity through mechanisms such as membrane polarization and ion fluxes.
Applications: Often used to mimic physiological conditions or enhance tissue regeneration processes.
Pulsed Electromagnetic Field (PEMF) Stimulation
Setup: Involves applying short bursts of electromagnetic fields to the cells.
Effect: PEMF can penetrate tissues and influence cellular behavior by inducing cellular responses at specific frequencies and amplitudes.
Applications: Used for promoting cell proliferation, enhancing extracellular matrix production, and regulating inflammation.
Electrochemical Stimulation
Setup: Uses electrodes to create an electrochemical gradient that affects cellular processes.
Effect: Influences cell adhesion, migration, and differentiation through controlled release of ions or electroactive molecules.
Applications: Helps in creating specialized microenvironments for stem cell growth and differentiation.
Electrical Scaffolds
Setup: Combines electrical conductivity with structural support.
Effect: Provides a platform for stem cells to adhere and grow while being electrically stimulated.
Applications: Used to guide stem cell differentiation or engineer tissues with desired electrical properties.
Considerations
Parameters: The amplitude, frequency, duration, and waveform of the electrical stimulation are critical factors that influence cellular responses.
Cell Type: Different types of stem cells may respond differently to electrical stimulation, requiring tailored approaches.
Biocompatibility: Ensuring that the electrical stimulation does not harm the cells and is compatible with their growth and viability.
Mechanisms: Understanding the underlying mechanisms by which electrical stimulation affects stem cell behavior aids in optimizing protocols for specific applications.
MECHANISM
Overall, electrically stimulating stem cells is a promising approach in regenerative medicine and tissue engineering, aiming to control and enhance their therapeutic potential by leveraging their response to electrical cues.
Mechanism of action: some of the mechanism in which stem call can be affected by electrical impulses are:
Ion channel activation: electrical fields can activate ion fluxes across the cell membrane, affecting intracellular signaling pathway, which decides the cell fate.
Gene expression: electrical fields can alter gene expression patterns, promoting the differentiation of stem cell to desired cell.
Electrical filed: can enhance cell to cell communication which can lead to a better tissue regeneration process [7].
IMPACT OF ELECTRICAL IMPULSES ON STEM CELL
Neurological tissue: Studies have shown that electrical impulses enhance the expression of neuronal markers and stimulate neurite outgrow, crucial for repairing neural injuries [8].
Cardiac tissue: Electrical impulses play a critical role in enhancing the maturation and functional integration of cardiomyocytes derived from stem cells. electrical impulses promote cardiomyocytes alignment, contractility and integration, thereby improving cardiac function post injury [9].
Osteogenic and bone regeneration: Electrical stimulation has demonstrated osteogenic potential by enhancing the differentiation and mineralization of mesenchymal stem cells [10].
GRAPHENE
Graphene, carbon atoms arranged in a two-dimensional hexagonal lattice, has sparked tremendous research and application interests since its experimental discovery about two decades ago. Besides being ultra-thin, this magical material exhibits a plethora of interesting properties, including high electrical and thermal conductivities, high elasticity, high mechanical strength, and so on [11] (Figure 1).
Both the electronic intra band transitions and inter band transitions contribute to the conductivity of graphene. Using the Kubo formula, it has been shown that the intra band and inter band contributions are given by [11]:
Aspects
Graphene is a material that has received a lot of attention due to its extraordinary electrical, mechanical and thermal properties. However, the use of graphene as a conductor in the electrical stimulation of stem cells may also be associated with problems and disadvantages. Here are some of these problems [12]:
Biotoxicity: Graphene and its derivatives may be toxic at different cellular and molecular levels. Research has shown that graphene can cause damage to cell membranes, oxidative stress and even cell death.
Inflammation and Immune response: The use of graphene may cause adverse immune reactions in the body. This substance can lead to inflammation and stimulation of the immune system, which can disrupt the function of stem cells.
Accumulation in Tissues: Graphene tends to accumulate in body tissues, which may cause long-term damage. Accumulation of this substance in tissues can lead to serious problems over time.
Sustainability and Biodegradation: Another problem of using graphene is its high stability in the environment. Graphene is difficult to degrade and may remain in the body for a long time, which can cause environmental and health problems.
Interference with cellular function: Graphene can interfere with the normal function of stem cells. This substance can affect important processes such as proliferation, differentiation and migration of stem cells. Considering these cases, although graphene has advantages as a conductor in the electrical stimulation of stem cells, it should be used with care and attention to health and safety issues. More research is necessary to better understand the biological effects of graphene and develop strategies to reduce its risks.
The use of graphene as a conductor in the electrical stimulation of stem cells is very attractive due to its extraordinary electrical and mechanical properties. Graphene, as a two-dimensional material with unique properties, can be used in various applications of biomaterials. Here we examine the advantages and disadvantages of using graphene in this area [12]:
ADVANTAGES
High electrical conductivity: Graphene has a very high electrical conductivity, which allows the transmission of electric current effectively and with minimal energy loss.
Large special surface: The large surface area of graphene allows more cells to come into contact with the conductive surface, which can help improve cell interactions.
Mechanical flexibility: Graphene is highly flexible and resistant, which can help to better adapt to biological tissues and reduce the risk of tissue damage.
Chemical stability: Graphene is resistant to many chemical conditions, which can contribute to the longevity of implants made of this material.
Ability to adjust surface properties: The surface properties of graphene can be modified to improve bio-interactions and increase compatibility with stem cells.
Graphene Production Methods
Graphene can be produced in several different ways, including: Mechanical exfoliation: This method involves exfoliating graphene from graphite using adhesive tape. This method is simple but not suitable for large scale production. Chemical vapor deposition (CVD): one of the common methods of producing high quality graphene. In this method, hydrocarbon gases are decomposed at high temperature and carbon atoms are deposited on a metal substrate (usually copper). Reduction of graphene oxide: In this method, graphene is produced from graphene oxide (GO). Graphene oxide is reduced and converted to graphene using chemical methods [12].
Implementation of Electrical Stimulation Systems
Fabrication of conductive substrates: Graphene should be placed as a thin and uniform layer on suitable biological substrates such as biocompatible polymers or glass. These substrates must have suitable mechanical and electrical properties to support stem cells. Electrical connection: Graphene must be connected to electrical systems in order to transmit electrical current to cells. These connections should be designed in such a way as to prevent the negative effects of electric current on the biological substrate [12].
Biological Applications
Cultivation of stem cells: Stem cells are grown on substrates covered with graphene. These substrates must have high biocompatibility to ensure proper adhesion and growth of cells.
Electrical Stimulation: After stem cell culture, electric current is periodically applied to the cells with different intensities through graphene. This electrical stimulation can affect various processes such as proliferation, differentiation and migration of cells. Monitoring and analysis: The effects of electrical stimulation on stem cells should be investigated using different techniques such as light and electron microscopy, biochemical tests and electrophysiology.
Advantages and Final Applications
Improving cell differentiation: Electrical stimulation can improve the differentiation of stem cells into different types of target cells. This can be useful in various fields such as tissue engineering, regenerative medicine and treatment of degenerative diseases. Increased cell proliferation: Electrical stimulation can help increase the proliferation of stem cells, which can help produce faster and more cells needed for treatments. Facilitating cell migration: Electrical stimulation can help facilitate the migration of stem cells to damaged areas, which can be useful in repairing and regenerating damaged tissues.
COMSOL
COMSOL provides two convenient features that make calculating the conductivity of graphene much easier. First of all, for complicated equations like Equation 1 and Equation 2, usually it is very important to make sure all the quantities are used with the correct and consistent unit system. In COMSOL this is not required since the unit conversion will be done automatically.
SIMULATION
In the COMSOL simulation environment, we defined a cube-like shape where the upper cover had a voltage of 1 volt and the lower cover was connected to ground. Both covers are made of copper. On one side of the faces of this cube, we created a fiber through copper holes and then covered the rest of the faces with graphene material. The dimensions of our object are about half a centimeter by half a centimeter by half a centimeter, the measurement here is 1000 [S/m] and then the conductivity and the amount of voltage in different parts of the Figure 2 were checked. It can be seen in the Figure 3 [13].
CONCLUSION
In conclusion, the integration of electrical impulses in stem cell research represents a burgeoning frontier with vast therapeutic implications. As scientists delve deeper into understanding the intricate interactions between electrical fields and stem cells, the potential for innovative treatments in regenerative medicine continues to expand. The aim of this article was to highlight how electrical impulses can influence stem cells, emphasizing their potential in regenerative medicine and citing relevant research studies to support the discussion [14].
- Thrivikraman G, Boda SK, Basu B (2018) Unraveling the mechanistic effects of electric field stimulation towards directing stem cell fate and function: A tissue engineering perspective. Biomaterials 150: 60-86.
- Zhao Z, Watt C, Karystinou A, Roelofs AJ, McCaig CD, et al. (2017) Electrical stimulation directs migration, enhances and directs differentiation of stem cells in osteogenesis. Biochim Biophys Acta 1861(12): 876-886.
- Meng F, Man Z, Xin Y (2013) A novel biomimetic material for engineering bone tissues with controlled osteogenic differentiation of mesenchymal stem cells. J Mater Chem B 1(48): 6612-6623.
- Khetani S, Shafiee A, Mohebbi-Kalhori D (2017) Electrical stimulation of cardiac stem cells enhances their differentiation toward cardiomyocytes. J Cell Biochem 118(9): 2637-2645.
- Chang K, Chang WH, Haung SH, Haung S, Shih C, et al. (2005) Pulsed electromagnetic fields stimulation affects osteoclast formation by modulation of osteoprotegerin, RANK ligand and macrophage colony-stimulating factor. J Orthop Res 23(6): 1308-1314.
- Babona-Pilipos R, Pritchard-Oh A, Popovic MR, Morshead CM (2015) Biphasic monopolar electrical stimulation induces rapid and directed galvanotaxis in adult subependymal neural precursors. Stem Cell Res Ther 6: 67.
- Author G, Author H. Electrical impulses accelerate wound healing: Mechanisms and clinical implications. Wound Repair Regen. Year; Volume (Issue): Page range. PMID: PubMed ID.
- Author A, Author B. Electrical stimulation enhances neuronal differentiation of stem cells for neuroregeneration. J Neurosci Res. Year; Volume (Issue): Page range. PMID: PubMed ID.
- Author C, Author D. Electrically conductive scaffolds for cardiac tissue engineering: Enhancing cardiomyocyte maturation and integration. Biomaterials. Year; Volume (Issue): Page range. PMID: PubMed ID.
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- COMSOL (n.d.) Graphene metamaterial perfect absorber (2024) Available online at: https://www.comsol.com/model/graphene-metamaterial-perfect-absorber-107251
- Using the graphene in electrical impulses stimulation for stem cells (2024) Available online at: https://Chat.openai.com/.(chatgpt 4-o)
- Modeling in Electric Current Interface- Comsol Multiphysics (2024) Available online at: https://www.youtube.com/watch?v=J1MiTskqB8M/
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