Equine iPS cells and their ability to enhance tendon regeneration in vivo

马 iPS 细胞及其增强体内肌腱再生的能力

基本信息

批准号：
8654299
负责人：
Lauren Virginia Schnabel
金额：
$ 12.61万
依托单位：
NORTH CAROLINA STATE UNIVERSITY RALEIGH
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8654299
关键词：
Acute Adult Aftercare Alkaline Phosphatase Allogenic Animals Antibody Formation Autologous Biochemical Biological Biological Assay Biology Cell Line Cell Transplantation Cell physiology Cells Chromosomes Clinical Dermal Disease Doctor of Philosophy Doxycycline Environment Equus caballus Exhibits Fibroblasts Flexor Flow Cytometry Gene Expression Profile Generations Genetic Haplotypes Histology Human Image Immune Immune response Immunohistochemistry Immunology Infiltration Inflammatory Response Injection of therapeutic agent Injury Investigation Knowledge Laboratories Laboratory Research Learning Lentivirus Vector Lesion Leukocytes MHC Class I Genes Magnetic Resonance Imaging Mentors Mesenchymal Stem Cells Methods Mixed Lymphocyte Culture Test Modeling Molecular Molecular Profiling Morphology Mus Orthopedics Pathologic Phase Phase Transition Pluripotent Stem Cells Preparation Property Qualifying Records Regenerative Medicine Research Research Personnel Sample Size Scientist Serum Specialty Boards Staging Staining method Stains Stem cells Surgeon System Techniques Tendinitis Tendon structure Teratoma Testing Therapeutic TimeLine Tissues Toll-like receptors Training Training Programs Transplantation Ultrasonography Universities Veterinarians Viral Work c-myc Genes career cell type clinically relevant cytokine expectation fetal graduate student immunogenic in vivo in vivo Model in vivo regeneration induced pluripotent stem cell insight knowledge base molecular marker regenerative repaired research study response skills stem cell biology stem cell therapy tissue regeneration transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): This application seeks support for a specialty board certified (ACVS) equine veterinarian to complete the final stages of preparation for her career as a translational clinical scientist in the fields of stem cell biology and regenerative medicine. Th applicant will work in the Cornell University induced Pluripotent Stem (iPS) Cell Core Laboratory under the guidance of the her mentor, Dr. Lisa A. Fortier, and collaborator, Dr. John C. Schimenti. Dr. Fortier is a scientist and large animal orthopedic surgeon who is well established in the fields of tendon repair and stem cell therapies. Dr. Schimenti is regarded as an expert in the fields of genetics and stem cell biology. Both have outstanding records for training graduate students and mentoring postdoctoral candidates and the overall research environment at Cornell is unique and eminently qualified to train translational scientists. The proposal is divide into two phases, a mentored phase and a transition phase into an independent research investigator. During Phase I, the applicant will complete her Ph.D. and seek to broaden her knowledge base and skill set to develop a deeper understanding of the basic biology of iPS cells, including their immunogenic and immunomodulatory properties compared to mesenchymal stem cells (MSCs). The applicant and her mentor have assembled a team of immunology collaborators, Drs. Douglas Antczak, Julia Felippe (Flaminio), and Cynthia Leifer, to advise the applicant during this mentored phase and help her learn the valuable immunology concepts and methods needed to complete these studies and understand their biological significance. In Phase II the applicant will apply the knowledge and skills learned in Phase I to complete a proof-of- principle in vivo study examining the early and late biological responses of diseased tendon to iPS cell and MSC treatment and the regenerative potential of iPS cells and MSCs for tendon repair. For these studies, we will use the well established equine model of tendonitis which has been extensively used by our research group. These experiments will test the hypothesis that iPS cells will have similar immunogenic and immunomodulatory properties as MSCs but superior regenerative potential because they are pluripotent stem cells whereas MSCs are not. This information is clinically important for determining which stem cell type should be applied therapeutically in the treatment of tendon diseases. The expectation of this proposal is that the applicant will gain the necessary laboratory research, scientific, and management skills necessary to establish a niche in the field of regenerative medicine as an independent clinician scientist in an academic environment.

描述（由申请人提供）：本申请寻求对专业委员会认证（ACVS）马兽医的支持，以完成她作为干细胞生物学和再生医学领域的转化临床科学家职业生涯的最后阶段的准备。申请人将在导师Lisa A. Fortier博士和合作者John C. Schimenti博士的指导下在康奈尔大学诱导多能干（iPS）细胞核心实验室工作。 Fortier 博士是一位科学家和大型动物整形外科医生，在肌腱修复和干细胞治疗领域颇有建树。 Schimenti 博士被认为是遗传学和干细胞生物学领域的专家。两者在培养研究生和指导博士后候选人方面都有着出色的记录，康奈尔大学的整体研究环境是独一无二的，非常适合培养转化科学家。该提案分为两个阶段：指导阶段和成为独立研究调查员的过渡阶段。在第一阶段，申请人将完成她的博士学位。并寻求扩大她的知识基础和技能，以更深入地了解 iPS 细胞的基础生物学，包括与间充质干细胞 (MSC) 相比，它们的免疫原性和免疫调节特性。申请人和她的导师组建了一个免疫学合作者团队，博士。 Douglas Antczak、Julia Felippe (Flaminio) 和 Cynthia Leifer 在指导阶段为申请人提供建议，帮助她学习完成这些研究所需的有价值的免疫学概念和方法，并了解其生物学意义。在第二阶段，申请人将应用第一阶段学到的知识和技能来完成原理验证体内研究，检查患病肌腱对 iPS 细胞和 MSC 治疗的早期和晚期生物反应，以及 iPS 细胞和 MSC 的再生潜力。用于肌腱修复的 MSC。在这些研究中，我们将使用我们的研究小组广泛使用的成熟的马肌腱炎模型。这些实验将检验以下假设：iPS 细胞具有与 MSC 类似的免疫原性和免疫调节特性，但具有卓越的再生潜力，因为它们是多能干细胞，而 MSC 则不是。该信息对于确定哪种干细胞类型应应用于肌腱疾病的治疗具有重要的临床意义。该提案的期望是申请人将获得必要的实验室研究、科学和管理技能，以在学术环境中作为独立的临床科学家在再生医学领域建立一个利基市场。