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Embryonic Stem Cell Models to Study the Axial Skeletal Lineage

研究中轴骨骼谱系的胚胎干细胞模型

基本信息

批准号：
7942892
负责人：
PETER MAYE
金额：
$ 20.68万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2011-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7942892
关键词：
Animals Biological Models Biology Bone Regeneration Brachyury protein Cartilage Cell model Cell physiology Cell surface Cells Chondrocytes Collaborations Collagen Core Facility Development ES Cell Line Embryo Embryonic Development Epiblast Epitopes Faculty Future Gene Expression Gene Targeting Generations Genes Genetic Genetic Population Study Genetic Recombination Goals Grant Growth Head Housing In Vitro Institution Knowledge Mesoderm Methodology Mind Mus NIH Program Announcements Osteoblasts Paraxial Mesoderm Parents Population Process Proteins Qualifying Reagent Reporter Reporter Genes Research Research Personnel Resources Role Science Sclerotome Signal Transduction Pathway Skeleton Source Staging Stem Cell Research Stem cells Testing Therapeutic Topaz Training Transgenic Mice Transgenic Organisms Transplantation Work adult stem cell base bone bone cell bone sialoprotein cell type embryonic stem cell in vivo infancy interest member novel osteochondral tissue pluripotency progenitor promoter public health relevance repaired skeletal skills stem tool

项目摘要

DESCRIPTION (provided by applicant): The central goal of our work is to use embryonic stem (ES) cells as a source from which to derive therapeutically relevant skeletal progenitor cells to treat conditions associated with bone and cartilage damage. The field of cell based therapeutics is largely at its infancy and enormous challenges lie ahead, including the ability to isolate specific cell types, maintain cells appropriately in culture, differentiate cells down a restricted lineage, and assess engrafted cell function after transplantation. There is an absolute need within this field to generate the necessary research tools to aid investigators in resolving these challenges. The process of differentiating ES cells into cartilage and bone, like embryonic development, will involve several intermediate differentiation steps and currently it is unknown at what point in the differentiation process will the ideal progenitor cell population(s) exist. Therefore, it will be critical to test and compare different progenitor cell populations that transiently form within a lineage for their capacity to differentiate into chondrocytes and osteoblasts upon transplantation. The aims of this proposal are focused on identifying and testing progenitor cell types of the axial skeleton lineage. To carry this out, we propose to generate fluorescent protein reporter ES cell lines that will mark progenitor and mature skeletal cell types. Aim1 focuses on generating a three fluorescent protein reporter ES cell line to distinctly identify cell types for early mesoderm, presomitic paraxial mesoderm, and sclerotome allowing us to study axial skeletal progenitor cell formation. Aim2 will generate ES cell lines that will couple different axial skeletal progenitor markers with a chondrocyte/osteoblast ES cell line thus enabling us to test and compare the ability to differentiate progenitor cell types to differentiate into cartilage and bone cells upon transplantation. PUBLIC HEALTH RELEVANCE: The aims of this application are focused on the study and testing of embryonic stem (ES) cell derived axial skeletal progenitor cells. We propose to generate novel ES cell lines that use fluorescent protein reporters to aid in the identification of progenitor and mature skeletal cell types of the cartilage and bone lineage. These ES cell lines will allow us to study the formation of axial skeletal progenitor cells and test their ability to differentiate into bone and cartilage upon transplantation. The reagents developed from this grant will have an important impact on therapeutic approaches involving the use ES cells to repair damaged cartilage and bone.

描述（由申请人提供）：我们工作的中心目标是使用胚胎干（ES）细胞作为来源，从该来源获得治疗相关的骨骼祖细胞以治疗与骨和软骨损伤相关的病症。基于细胞的治疗领域在很大程度上处于起步阶段，面临着巨大的挑战，包括分离特定细胞类型，在培养中适当维持细胞，使细胞分化为有限的谱系，以及评估移植后的移植细胞功能的能力。这一领域绝对需要产生必要的研究工具，以帮助调查人员解决这些挑战。ES细胞分化成软骨和骨的过程，如胚胎发育，将涉及几个中间分化步骤，目前尚不清楚在分化过程中的什么时候会存在理想的祖细胞群。因此，测试和比较在谱系内瞬时形成的不同祖细胞群体在移植后分化成软骨细胞和成骨细胞的能力将是至关重要的。该提案的目的是重点识别和测试轴向骨骼谱系的祖细胞类型。为了实现这一点，我们建议产生荧光蛋白报告ES细胞系，将标记祖细胞和成熟的骨骼细胞类型。Aim 1的重点是产生一个三荧光蛋白报告ES细胞系，以明确识别早期中胚层，presomitic近轴中胚层和sclerotome的细胞类型，使我们能够研究轴向骨骼祖细胞的形成。Aim 2将产生ES细胞系，其将不同的轴向骨骼祖细胞标志物与软骨细胞/成骨细胞ES细胞系偶联，从而使我们能够测试和比较分化祖细胞类型以在移植后分化成软骨和骨细胞的能力。公共卫生关系：本申请的目的集中于胚胎干（ES）细胞衍生的中轴骨骼祖细胞的研究和测试。我们建议产生新的ES细胞系，使用荧光蛋白报告，以帮助识别祖细胞和成熟的骨骼细胞类型的软骨和骨谱系。这些ES细胞系将使我们能够研究中轴骨骼祖细胞的形成，并测试它们在移植后分化成骨和软骨的能力。从这笔赠款中开发的试剂将对涉及使用ES细胞修复受损软骨和骨骼的治疗方法产生重要影响。