Non-Thermal Plasma in Biomedicine: A New Paradigm for Redox Cell Activation

生物医学中的非热等离子体：氧化还原细胞激活的新范例

• 批准号: 8075299
• 负责人: Theresa A Freeman
• 金额: $ 35.94万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8075299
• 关键词: Adipose tissue; Allogenic; Allografting; Antioxidants; Biological; Biological Models; Biological Sciences; Biology; Bone Marrow; Cell Differentiation process; Cell Proliferation; Cell physiology; Cells; Chondrogenesis; Clinical; Clinical Research; Collaborations; Development; Devices; Electrons; Embryonic Structures; Endothelial Cells; Engineering; Engraftment; Gene Expression; Generations; Genes; Goals; Healed; Histology; Institutes; Knowledge; Lasers; Length; Life; Link; Measures; Mediating; Mesenchymal Stem Cells; Methods; Microscopy; Molecular; Nitrogen; Nodule; Operative Surgical Procedures; Osteogenesis; Outcome Study; Oxidation-Reduction; Oxygen; Phenotype; Physics; Plasma; Property; Proteins; Publishing; Reactive Nitrogen Species; Reactive Oxygen Species; Regenerative Medicine; Regulation; Reporting; Signal Pathway; Signal Transduction; Stem cells; System; Technology; Testing; Time; Tissue Engineering; Tissues; United States; Universities; Vascular Graft; Vascularization; Work; Wound Healing; adult stem cell; base; cancer cell; healing; implantation; improved; in vivo; insight; new technology; novel strategies; osteogenic; precursor cell; scaffold; stem cell biology; stem cell differentiation; stem cell fate; tissue regeneration; tool; transcription factor; treatment duration; vascular tissue engineering

DESCRIPTION (provided by applicant): Non-thermal dielectric barrier discharge plasma (NT-Plasma) is a relatively new physics-based technology. Although there are few reports concerning the application of this technology to biological sciences, it is known that NT-plasma influences cell function mainly through activation of reactive oxygen and nitrogen species (ROS/RNS) signaling pathways. In collaboration with the Drexel Plasma Institute, arguably the foremost experts in the field of plasma physics in the United States, we propose to use NT-plasma as a tool to specifically manipulate cellular redox to promote MSC commitment and differentiation. The proposed study is based on recent observations that the NT-Plasma system promotes reactive oxygen species generation enhances development of embryonic structures and initiates the expression of many genes linked to cell differentiation. The first Specific Aim is to delineate the mechanism by which NT-Plasma generated ROS/RNS promotes MSC proliferation, commitment and differentiation; while simultaneously developing the NT-Plasma device for this application. We will test the hypothesis that NT-Plasma enhances stem cell differentiation along chondrogenic, endothelial and osteogenic lineages. Moreover, that this effect is mediated via ROS/RNS dependent signaling pathways that serve to influence the cell's oxidative state. To test this hypothesis, first, we will define the conditions that permit NT-Plasma to regulate the oxidative state of the cell. At the same time, we will fine tune the NT-Plasma system modulating the length of treatment, times of treatment and amplitude and discharge parameters. We will measure ROS and RNS, the redox status of the cells, the expression and activity of antioxidant proteins, as well as responsive signaling pathways. The second Specific Aim is to determine how NT-Plasma advances differentiation of progenitor cells in two model systems, an endochondral ossification system and a tissue engineered vascular tissue allograft. We propose to test the hypothesis that NT-Plasma positively influences stem cell commitment and differentiation in vivo. Each system provides a unique opportunity to evaluate the potential and feasibility of NT plasma treatment to enhance tissue healing and replacement, while at the same time gaining valuable understanding of the resulting signaling networks. If the goals of this application are successfully achieved, then the knowledge gained in development of NT-Plasma technology will be of transformative scientific and clinical importance. NT-Plasma's ability to amplify stem cell function will be an invaluable tool for tissue engineering and regenerative medicine in general, and will provide new insights into the basic biology of ROS signaling in stem cell biology. PUBLIC HEALTH RELEVANCE: The purpose of this project is to explore and develop biological applications of Non-Thermal Plasma for use in tissue engineering and regenerative medicine. Our preliminary studies and other published reports indicate that this new technology can significantly influence the fate of adult stem cells and promote their proliferation, commitment and differentiation. Results generated from the proposed studies will provide improved methods for tissue repair and regeneration with direct applicability to both clinical research and surgical procedures.

描述（由申请人提供）：非热介质阻挡放电等离子体（NT-等离子体）是一种相对较新的基于物理的技术。尽管关于该技术在生物科学中的应用的报道很少，但已知NT-血浆主要通过活性氧和氮物质（ROS/RNS）信号通路的活化来影响细胞功能。与德雷克塞尔等离子体研究所合作，可以说是美国等离子体物理学领域最重要的专家，我们建议使用NT-等离子体作为一种工具，专门操纵细胞氧化还原，以促进MSC的承诺和分化。这项拟议的研究基于最近的观察结果，即NT-血浆系统促进活性氧的产生，增强胚胎结构的发育，并启动许多与细胞分化相关的基因的表达。第一个具体目标是描述NT-血浆产生的ROS/RNS促进MSC增殖、定型和分化的机制;同时开发用于该应用的NT-血浆装置。我们将检验NT-血浆增强干细胞分化沿着软骨，内皮和成骨谱系的假设。此外，这种作用是通过ROS/RNS依赖性信号通路介导的，该信号通路用于影响细胞的氧化状态。为了验证这一假设，首先，我们将定义允许NT-血浆调节细胞氧化状态的条件。同时，我们将微调NT-等离子体系统，调节治疗长度、治疗次数以及振幅和放电参数。我们将测量ROS和RNS，细胞的氧化还原状态，抗氧化蛋白的表达和活性，以及响应信号通路。第二个具体目标是确定NT-血浆如何在两个模型系统中促进祖细胞分化，即软骨内骨化系统和组织工程血管组织同种异体移植物。我们建议测试的假设，NT-血浆积极影响干细胞的承诺和分化在体内。每个系统都提供了一个独特的机会来评估NT等离子体治疗的潜力和可行性，以增强组织愈合和替换，同时获得对所产生的信号网络的有价值的理解。如果成功实现了本申请的目标，那么在NT-Plasma技术开发过程中获得的知识将具有变革性的科学和临床重要性。NT-Plasma放大干细胞功能的能力将成为组织工程和再生医学的宝贵工具，并将为干细胞生物学中ROS信号传导的基础生物学提供新的见解。 公共卫生相关性：本计画的目的是探讨及发展非热电浆在组织工程及再生医学上的生物应用。我们的初步研究和其他已发表的报告表明，这项新技术可以显着影响成体干细胞的命运，并促进其增殖，承诺和分化。从拟议的研究中产生的结果将提供用于组织修复和再生的改进方法，直接适用于临床研究和外科手术。