The Characterization of the Skeletogenic Stem Cells that Contribute to Post Natal Axial Skeletal Tissue Repair

有助于产后中轴骨骼组织修复的成骨干细胞的表征

• 批准号: 9288127
• 负责人: Beth Christie Bragdon
• 金额: $ 9.02万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-06 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9288127
• 关键词: Applied Research; Basic Science; Biochemistry; Biological Process; Biology; Biophysics; Bone Marrow; Bone Marrow Stem Cell; Bone Matrix; Bone Regeneration; Bone Surface; Bone Tissue; Bone Transplantation; Bone callus; Boston; Burn injury; Cartilage; Cell Lineage; Cells; Clinical; Communication; Competence; Core Facility; Data; Defect; Development; Development Plans; Discipline; Engineering; Environment; Event; FDA approved; Faculty; Fatty acid glycerol esters; Femur; Fluorescence-Activated Cell Sorting; Fracture; Fracture Healing; Genes; Genetic Transcription; Goals; Heterotopic Ossification; Human; Impaired wound healing; Implant; In Vitro; Injury; Joints; Knowledge; Label; LacZ Genes; Lead; Leadership; Learning; Limb structure; Literature; Location; Marrow; Mentors; Mesenchymal Stem Cells; Microarray Analysis; Modeling; Molecular Biology; Morbidity - disease rate; Mus; Muscle; Natural regeneration; Operative Surgical Procedures; Orthopedic Surgery procedures; Osteogenesis; Pain; Periosteum; Physiologic Ossification; Population; Postdoctoral Fellow; Property; Publications; Recovery; Recruitment Activity; Reporter; Reporting; Research; Research Personnel; Resources; Running; Science; Scientist; Site; Skeleton; Smooth Muscle Actin Staining Method; Source; Stem cells; Surface; Tamoxifen; Technical Expertise; Testing; Therapeutic; Time; Tissues; Total Hip Replacement; Training; Transgenic Mice; Transgenic Organisms; Transplanted tissue; Trauma; Traumatic injury; Universities; Woman; base; bone; bone morphogenetic protein 2; career; career development; cell type; cost; craniofacial; demineralization; differential expression; embryonic stem cell; experience; gene complementation; healing; implantation; improved; in vivo; interest; knowledge base; limb amputation; member; mouse model; multidisciplinary; osteogenic; prevent; progenitor; promoter; public health relevance; repaired; response; responsible research conduct; skeletal; skeletal tissue; skills; soft tissue; stem; stem cell differentiation; stem cell population; tissue repair; tissue trauma; transcription factor

 DESCRIPTION (provided by applicant): Candidate: Dr. Bragdon's training has been multidisciplinary encompassing biochemistry, molecular biology, and biophysics. During her research career she developed an interest in skeletal biology which she furthered by joining Dr. Gerstenfeld's lab and moving these interests into in vivo bone repair and regeneration models. Dr. Bragdon's long term goal is to become an independent researcher in an academic environment, pursuing basic and applied research in skeletal tissue biology to identify mechanisms that can be exploited as treatment for heterotrophic ossification, to advance current bone grafting materials, and to improve bone regeneration. In order to obtain these goals a career development plan has been developed by Drs. Gerstenfeld and Morgan, along with a co-mentor committee who will assist Dr. Bragdon as she transitions to an independent career. The mentor committee consists of both basic scientists and clinicians who will be able to provide clinical perspectives, interdisciplinary knowledge base, and independent advice. During this time additional research skills will be learned, specifically Fluorescence Activated Cell Sorting and microarray analysis. Equally balanced with learning of new technical skills will be professional development which is based on the National Postdoctoral Association Core Competencies and includes: communication, leadership and management, discipline-specific conceptual knowledge, professional skills, and responsible conduct of research. Resources available at Boston University will greatly aid in the career development of Dr. Bragdon. She will have access to core facilities run by faculty and staff members for technical advice, professional development through the Office of Professional development and Post-doctoral Affairs, BU Broadening Experiences in Scientific Training (BEST), Women in Science and Engineering, and Women in Networks. Research: Fractures are one of the most traumatic injuries that can occur in humans with 8 to 10 million fractures occurring annually which approximately 10% results in delayed or impaired healing. Repair is dependent upon the recruitment of mesenchymal stem cells (MSCs) to the injury site followed by a cascade of events resulting in the formation of cartilage and bone. A similar event can also occur in soft tissue due to trauma, burns, and total hip replacements resulting in boney tissue called ectopic or heterotopic ossification (HO). Multiple stem cell populations from the bone surface and muscle have been suggested to be involved however it is unclear as to the specific population of skeletogenic stem cells that are recruited or their location. Based on previous data the hypothesis of this proposal is that there i a "universal MSC" with in the axial limb tissues that contributes to injury induced bone formation. The aims of this proposal will 1) determine the stem cell contribution from the bone surface and muscle to the HO and identify whether the stem cell populations are similar, 2) determine the impact of muscle trauma has on the populations of recruited stem cells, and 3) determine the transcriptional machinery of these stem cell populations. In this proposal demineralized bone matrix will be implanted into inducible transgenic reporter mice models to induce ectopic bone formation. The mouse models will allow for the specific labeling and capturing of the different populations of cells known to induce during fracture and ectopic bone formation.

 描述（由适用提供）：候选人：Bragdon博士的培训是多学科的，包括生物化学，分子生物学和生物物理学。在她的研究生涯中，她对骨骼生物学产生了兴趣，她加入了Gerstenfeld博士的实验室并将这些兴趣转移到体内骨修复和再生模型中。 Bragdon博士的长期目标是成为学术环境中的一名独立研究人员，从事骨骼组织生物学的基本和应用研究，以识别可以探索的机制，这些机制可以作为异营养骨化的治疗方法，以提高当前的骨移植材料，并改善骨再生。为了获得这些目标，博士已经制定了职业发展计划。格斯滕菲尔德（Gerstenfeld）和摩根（Morgan）以及一个委员会委员会将协助布拉格登（Bragdon）博士过渡到独立职业。导师委员会由基础科学家和临床医生组成，他们将能够提供临床观点，跨学科知识库和独立建议。在此期间，将学习其他研究技能，特别是荧光激活的细胞分选和微阵列分析。与新技术技能的学习同样平衡将是基于国家博士后协会核心竞争力的专业发展，包括：沟通，领导和管理，特定学科的概念知识，专业技能和负责任的研究行为。波士顿大学可用的资源将极大地帮助布拉格博士的职业发展。她将可以通过教职员工和工作人员运营的核心设施，通过专业发展和博士后事务办公室，科学培训（BEST），科学和工程领域的妇女以及网络中的妇女的经验，通过专业发展和博士后的专业发展，专业发展。研究：骨折是每年发生8至1000万个分数的人类可能发生的最创伤的损伤之一，大约10％会导致延迟或受损的愈合。修复取决于间充质干细胞（MSC）募集到损伤部位，然后是一系列事件，导致软骨和骨骼形成。由于创伤，燃烧和总髋关节置换，导致骨组织称为Ecopic或异位骨化（HO），在软组织中也可能发生类似的事件。已经提出了来自骨表面和肌肉的多个干细胞群体涉及，但是对于被募集的骨骼发育干细胞的特定群体或其位置而言，尚不清楚。基于先前的数据，该提案的假设是在轴向肢体时机中有一个“通用MSC”，这导致损伤引起的骨骼形成。 该提案的目的是1）确定干细胞从骨表面和肌肉对HO的贡献，并确定干细胞群体是否相似，2）确定肌肉创伤对招募干细胞的群体的影响，3）确定这些干细胞群体的转录机械。在此提案中，绝望的骨基质将植入可诱导的转基因记者小鼠模型中，以诱导生态骨形成。小鼠模型将允许在裂缝和异位骨形成过程中已知会诱导的不同细胞种群的特定标记和捕获。