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Global Translational Medicine                                      Electrical stimulation in therapy and biology

























                                   Figure 3. Mechanisms of action and clinical applications of electrical stimulation
            ES contributed to improved tissue remodeling, repair, and   and tissue remodeling.  E S enhances these processes
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            therapeutic outcomes. Recent studies have expanded our   by modulating  the interaction  with adhesion molecules
            understanding of these processes, integrating established   and regulating the cytoskeletal rearrangements. Studies
            and emerging insights into ES’s mechanism of action.  involving low-amplitude direct current fields suggest that
                                                               increased receptor proteins and focal adhesion kinase
            3.1. Activation of signaling pathways              proteins are necessary for cell adhesion and migration into
            ES activates intracellular signaling by modulating the   the extracellular matrix. 4
            electrical and chemical milieu of the cells. Based on   The movement of cells in response to ES is referred to
            the signals from applied electric fields, voltage-gated   as galvanotaxis or electrotaxis. When the field strength
            ion channels allow Ca²  to enter the cells and initiate a   is optimized, various cell types, such as keratinocytes,
                               +
            sequence of intracellular signals. Recent research stresses   fibroblasts, and even immune cells, exhibit directed
            that specific ion channels, including aquaporins, mediate   migration toward the cathode. These observations are
            ES’s effects. For example, alternating current stimulation   derived  from  studies  using  capacitive  coupling  systems,
            increases the number of open aquaporin channels without   which create homogenous electric fields. Such stimulation
            altering the membrane potential, providing evidence for a   promotes cell migration and increases the deposition of
            selective mechanism of cell hydration and ion transport. 30  glycosaminoglycans and extracellular matrix components.
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              Furthermore, ES activates the mitogen-activated   These findings are clinically valuable, offering promising
            protein kinase/extracellular signal-regulated kinase   strategies for improving tissue repair.
            and phosphatidylinositol 3 kinase/protein kinase B for
            cell survival and proliferation. Studies using pulsed   3.3. Influence on growth and differentiation
            electromagnetic field stimulation have shown the   ES modulates stem cell behavior and fate by recreating
            possibility of modulating oxidative stress by reducing   physiological electrical signals. For instance, biphasic
            reactive oxygen species levels and increasing antioxidant   waveforms  commonly  used  in  tissue  engineering  of  the
            markers such as superoxide dismutase. This dual effect   neural system enhance the differentiation of neural stem
            contributes to maintaining cellular stability in physiological   cells into neurons with increased neurite length and
            and therapeutic states.  Recent research also shows that ES   branching points. Conductive scaffolds improve this impact
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            plays a role in angiogenesis and inflammation by regulating   by creating favorable conditions for neural regrowth.
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            transcription factors such as hypoxia-inducible factor   Similarly, mesenchymal stem cells undergoing pulsed ES
            1-alpha and nuclear factor kappa beta. These pathways   have a higher osteogenic differentiation outcome. Previous
            enhance cellular metabolism and repair. Notably, the   studies have shown that runt-related transcription
            ability of ES to target hypoxic or damaged cells suggests   factor 2 and osteopontin as essential biomarkers that are
            its potential utility in treating ischemia or chronic wounds.  upregulated during this process.  Furthermore, culturing
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                                                               cells with biochemical signals such as sulfated hyaluronan,
            3.2. Cell adhesion and migration                   combined with pulsed electromagnetic field stimulation,
            Cell adhesion and migration are essential in various   can boost bone matrix development, offering a novel
            processes, such as wound healing, immune response,   strategy for orthopedic medicine. 36


            Volume 4 Issue 3 (2025)                         26                              doi: 10.36922/gtm.7774
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