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

• 批准号: 8463124
• 负责人: Lauren Virginia Schnabel
• 金额: $ 2.09万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2013-08-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8463124
• 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

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的职业生涯的最后准备阶段。申请人将在其导师丽莎博士的指导下在康奈尔大学诱导多能干细胞核心实验室工作。Fortier和合作者John C. Schimenti 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享有盛誉。Schimenti博士被认为是遗传学和干细胞生物学领域的专家。两者都有培养研究生和指导博士后候选人的出色记录，康奈尔大学的整体研究环境是独特的，非常适合培养翻译科学家。该提案分为两个阶段，一个是指导阶段，另一个是向独立研究调查员过渡阶段。 在第一阶段，申请人将完成博士学位。并寻求扩大她的知识基础和技能，以发展iPS细胞的基础生物学的更深入的理解，包括其免疫原性和免疫调节特性相比，间充质干细胞（MSC）。申请人和她的导师组建了一个免疫学合作者团队，道格拉斯Antczak博士、Julia Felippe（Flaminio）博士和Cynthia Leifer博士，在此指导阶段为申请人提供建议，并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，申请人将应用在第一阶段学到的知识和技能，完成一项原理验证体内研究，检查患病肌腱对iPS细胞和MSC治疗的早期和晚期生物学反应，以及iPS细胞和MSC用于肌腱修复的再生潜力。对于这些研究，我们将使用我们研究小组广泛使用的已建立的马肌腱炎模型。这些实验将检验iPS细胞将具有与MSC相似的免疫原性和免疫调节性质但具有上级再生潜力的假设，因为它们是多能干细胞，而MSC不是。这一信息对于确定哪种干细胞类型应该在治疗肌腱疾病的治疗中应用具有临床重要性。 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利基。