Search Results
Medical Gas Plasma Jet Technology Targets Murine Melanoma in an Immunogenic Fashion
Medical technologies from physics are imperative in the diagnosis and therapy of many types of diseases. In 2013, a novel cold physical plasma treatment concept was accredited for clinical therapy. This gas plasma jet technology generates large amounts of different reactive oxygen and nitrogen species (ROS). Using a melanoma model, gas plasma technology is tested as a novel anticancer agent. Plasma technology derived ROS diminish tumor growth in vitro and in vivo. Varying the feed gas mixture modifies the composition of ROS. Conditions rich in atomic oxygen correlate with killing activity and elevate intratumoral immune-infiltrates of CD8+ cytotoxic T-cells and dendritic cells. T-cells from secondary lymphoid organs of these mice stimulated with B16 melanoma cells ex vivo show higher activation levels as well. This correlates with immunogenic cancer cell death and higher calreticulin and heat-shock protein 90 expressions induced by gas plasma treatment in melanoma cells. To test the immunogenicity of gas plasma treated melanoma cells, 50% of mice vaccinated with these cells are protected from tumor growth compared to 1/6 and 5/6 mice negative control (mitomycin C) and positive control (mitoxantrone), respectively. Gas plasma jet technology is concluded to provide immunoprotection against malignant melanoma both in vitro and in vivo.
Hyperspectral Imaging of Wounds Reveals Augmented Tissue Oxygenation following Cold Physical Plasma Treatment in Vivo
Efficient vascularization of skin tissue supports wound healing in response to injury. This includes elevated blood circulation, tissue oxygenation, and perfusion. Cold physical plasma promotes wound healing in animal models and humans. Physical plasmas are multicomponent systems that generate several physicochemical effectors, such as ions, electrons, reactive oxygen and nitrogen species, and UV radiation. However, the consequences of plasma treatment on wound oxygenation and perfusion, vital processes to promote tissue regeneration, are largely unexplored. We used a novel hyperspectral imaging (HSI) system and a murine dermal full-thickness wound model in combination with kINPen argon plasma jet treatment to address this question. Plasma treatment promoted tissue oxygenation in superficial as well as deep (6 mm) layers of wound tissue. In addition to perfusion changes, we found a wound healing stage-dependent shift of tissue hemoglobin and tissue water index during reactive species-driven wound healing. Contactless, fast monitoring of medical parameters in real-time using HSI revealed a plasma-supporting effect in wound healing together with precise information about biological surface-specific features.
Nrf2 signaling and inflammation are key events in physical plasma-spurred wound healing
Wound healing is strongly associated with the presence of a balanced content of reactive species in which oxygen-dependent, redox-sensitive signaling represents an essential step in the healing cascade. Numerous studies have demonstrated that cold physical plasma supports wound healing due to its ability to deliver a beneficial mixture of reactive species directly to the cells. Methods: We described a preclinical proof-of-principle-concept of cold plasma use in a dermal, full-thickness wound model in immunocompetent SKH1 mice. Quantitative PCR, Western blot analysis, immunohistochemistry and immunofluorescence were perfomed to evaluate the expression and cellular translocation of essential targets of Nrf2 and p53 signaling as well as immunomodulatory and angiogenetic factors. Apoptosis and proliferation were detected using TUNEL assay and Ki67 staining, respectively. Cytokine levels in serum were measured using bead-based multiplex cytokine analysis. Epidermal keratinocytes and dermal fibroblasts were isolated from mouse skin to perform functional knockdown experiments. Intravital fluorescence analysis was used to illustrate and quantified microvascular features. Results: Plasma exerted significant effects on wound healing in mice, including the promotion of granulation and reepithelialization as a consequence of the migration of skin cells, the balance of antioxidant and inflammatory response, and the early induction of macrophage and neutrophil recruitment to the wound sites. Moreover, through an early and local plasma-induced p53 inhibition with a concomitant stimulation of proliferation, the upregulation of angiogenetic factors, and an increased outgrowth of new vessels, our findings explain why dermal skin repair is accelerated. The cellular redox homeostasis was maintained and cells were defended from damage by a strong modulation of the nuclear E2-related factor (Nrf2) pathway and redox-sensitive p53 signaling. Conclusions: Although acute wound healing is non-problematic, the pathways highlighted that mainly the activation of Nrf2 signaling is a promising strategy for the clinical use of cold plasma in chronic wound healing.