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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

基本信息

批准号：
9109739
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
项目类别：
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/9109739
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 Trauma Cartilage Cell Lineage Cells Clinical Communication Complement Core Facility Data Defect Development Development Plans Discipline Engineering Environment Equilibrium Event FDA approved Faculty Fatty acid glycerol esters Femur Fluorescence-Activated Cell Sorting Fracture Fracture Healing Genes Goals Healed 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 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 cost craniofacial differential expression embryonic stem cell experience 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

项目摘要

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.