Tissue engineered skeletal muscle delivering a myokine protein to treat volumetric muscle loss

组织工程骨骼肌提供肌因子蛋白以治疗体积肌肉损失

• 批准号: 9769782
• 负责人: Peter Hong Ung Lee
• 金额: $ 13.31万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2020-06-12
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9769782
• 关键词: Ablation; Adopted; Affect; American; American College of Surgeons; Appointment; Attenuated; Autologous; Award; Biochemical; Biological Models; Biology; Biomedical Engineering; Blood Circulation; Cell membrane; Clinical; Collaborations; Combined Modality Therapy; Country; Data; Defect; Development; Disease; Doctor of Philosophy; Doxycycline; Endocrine; Engineering; Ensure; Environment; Essential Genes; Foundations; Functional disorder; Funding; Future; Gene Delivery; Genetic; Goals; Grant; Growth; Healthcare; Healthcare Systems; Human; Implant; In Vitro; Injury; Institution; Joints; K-Series Research Career Programs; Laboratory Research; Lead; Longevity; Malignant - descriptor; Mediating; Medical; Medical center; Membrane; Mentors; Modeling; Molecular Biology; Mus; Muscle; Muscular Dystrophies; Myocardium; Myopathy; Names; Natural regeneration; Ohio; Operative Surgical Procedures; Pathology; Performance; Physiological; Physiology; Principal Investigator; Protein Chemistry; Proteins; Public Health; Quality of life; Recombinants; Recording of previous events; Regenerative Medicine; Research; Research Personnel; Research Training; Residencies; Role; Sarcolemma; Scientist; Series; Skeletal Muscle; Stem cell transplant; Stress; Surgeon; Testing; Therapeutic; Time; Tissue Engineering; Tissue Grafts; Tissues; Training; Transgenic Mice; Translational Research; Trauma; United States National Aeronautics and Space Administration; United States National Institutes of Health; Universities; Viral; Wild Type Mouse; base; cell type; clinical application; complement resource; effective therapy; experience; extracellular; healing; improved; in vitro Model; in vivo; injury and repair; innovation; live cell imaging; mouse model; muscle engineering; muscle physiology; muscle regeneration; neonate; novel; novel strategies; novel therapeutic intervention; oxidation; paracrine; patient mobility; professor; regenerative; repaired; response; sensor; skills; success; synergism; tenure track; therapeutic protein; tissue regeneration; tissue repair; tool; volumetric muscle loss

PROJECT SUMMARY Candidate: Dr. Lee is an Assistant Professor of Surgery on the tenure track at The Ohio State University, with a joint appointment in the Department of Biomedical Engineering. He is surgeon scientist and holds MD, PhD, MS, and MPH degrees, and has residency training in general and cardiothoracic surgery. He has extensive experience in the development and use of tissue-engineered skeletal muscle constructs and has recently been awarded grants from NASA and the American College of Surgeons as a Principal Investigator. His long-term goal is to become an independent investigator with a focus on translational research emphasizing the clinical applications of tissue-engineered skeletal and cardiac muscle constructs. Environment: The Ohio State University Wexner Medical Center is a top ranked academic institution with a strong commitment to research and training. The Department of Surgery is ranked #14 in the country in NIH funding with over $6 million in funding annually. The department is committed to supporting the growth of promising surgeon scientists such as Dr. Lee and has provided him with the necessary support to succeed, including a separate research laboratory and office space. He will be provided 75% protected research time as part of this K08 award. He is also surrounded by three senior and successful mentors, each of whom have a long track record of continuous NIH funding and history of successfully training young scientists to become independent investigators. Dr. Lee will have a full complement of resources available to him to ensure his success. Research: This innovative proposal seeks to combine 1) Dr. Lee's expertise in the novel use of tissue-engineered skeletal muscle BioArtifical Muscles (BAMs) as an in vitro muscle model and an in vivo platform for therapeutic protein delivery and replacement graft tissue, with 2) the use of a known effective tissue repair protein, to 3) treat volumetric muscle loss (VML), a significant surgical problem with limited therapeutic options. MG53 as a tissue repair protein serves essential roles in cell membrane repair. Genetic ablation of MG53 results in defective sarcolemma repair and muscle regeneration. When administered systemically, the recombinant human MG53 (rhMG53) protein protected traumatic muscle injury and also ameliorated the pathology associated with muscular dystrophy. The scientific goal of this project is centered on testing the hypothesis that “implantable BAMs can be engineered to secrete MG53 and enhance the tissue injury-repair and regeneration capacity associated with volumetric muscle loss”. In aim 1, he proposes to use BAMs as a model to elucidate the mechanism for MG53 secretion in response to tissue injury, and establish BAMs as a delivery vehicle for tailored secretion of MG53 to treat VML. In aim 2, he will establish the physiologic role of MG53 in muscle regeneration associated with VML and conduct proof- of-concept studies with BAM/MG53 combination to treat VML. Overall, he envisions that exploring the synergy between BAMs and MG53 will have substantial translational implications for developing a new therapeutic strategy for VML.

项目摘要 候选人：李博士是俄亥俄州州立大学的外科助理教授， 生物医学工程系的联合任命。他是外科医生科学家，拥有医学博士，博士， MS和MPH学位，并在普通和心胸外科住院医师培训。彼拥有丰富 在开发和使用组织工程化骨骼肌结构方面的经验， 作为首席研究员，他获得了美国宇航局和美国外科医生学院的赠款。他的长期 我的目标是成为一名独立的研究者，专注于翻译研究，强调临床 组织工程化骨骼肌和心肌构建的应用。环境：俄亥俄州 大学Wexner医学中心是一个顶级的学术机构，致力于研究 和培训及其有效外科系在NIH资助中排名全国第14位，拥有超过600万美元的资金。 每年资助。该部门致力于支持有前途的外科医生科学家的成长，如 博士李和提供了必要的支持，他成功，包括一个单独的研究实验室 和办公空间。作为K 08奖的一部分，他将获得75%的研究时间。他也是 周围有三位资深而成功的导师，他们中的每一位都有长期连续的NIH记录。 成功培训年轻科学家成为独立研究人员的资金和历史。李博士将 我们有足够的资源来确保他的成功。研究：这一创新的建议 旨在将联合收割机1）李博士在组织工程骨骼肌生物医学新用途方面的专业知识 肌肉（BAM）作为体外肌肉模型和用于治疗性蛋白质递送的体内平台， 置换移植组织，2）使用已知有效的组织修复蛋白，3）治疗肌肉体积 失活（VML）是一个重要的手术问题，治疗选择有限。MG 53作为组织修复蛋白， 在细胞膜修复中的重要作用。MG 53的基因切除导致有缺陷的肌膜修复， 肌肉再生当全身给药时，重组人MG 53（rhMG 53）蛋白 保护创伤性肌肉损伤，并改善与肌营养不良症相关的病理学。的 该项目的科学目标集中在测试“植入式BAM可以被设计成 分泌MG 53并增强与肌肉体积相关的组织损伤修复和再生能力 损失”。在目标1中，他建议使用BAM作为模型来阐明MG 53分泌的机制， 组织损伤，并建立BAM作为用于定制的MG 53分泌的递送载体以治疗VML。在目标2中， 他将建立MG 53在与VML相关的肌肉再生中的生理作用，并进行证明- BAM/MG 53联合治疗VML的概念研究。总的来说，他认为探索协同效应 BAM和MG 53之间的相互作用将对开发新的治疗药物具有实质性的转化意义。 VML战略。