Animal Models to Study Bone Marrow Mesenchymal Stem Cells

描述(申请人提供)：对于许多成人骨骼干细胞群体，我们缺乏在复杂的组织环境中识别它们并确定它们是否有助于骨骼组织修复的能力。无法在自然环境中研究成体干细胞是必须克服的一个关键障碍，以促进我们对它们如何促进再生过程的理解。在这里，我们主要关注骨髓间充质干细胞(BMSCs)，这是一种具有巨大治疗潜力的成体干细胞群体。可以使用小鼠的遗传方法，使我们能够识别和定位骨骼中的BMSCs。我们工作的最新进展已经确定了一种新的转基因报告基因动物模型，该模型可以识别骨髓中的BMSCs。这项提案的目标将继续描述这一动物模型，以确认我们的初步研究，并建立一个可诱导的Cre版本，使我们能够在体内绘制该细胞群体的命运图。总的来说，这些动物模型将使我们能够分析骨髓中存在的BMSCs的数量，并确定它们随着时间的推移对骨骼修复的贡献。 公共卫生相关性：骨髓间充质干细胞(BMSCs)是一种被广泛研究的成人干细胞群体，它保留了分化为不同骨骼细胞类型的能力。因此，骨髓间充质干细胞在骨组织修复中具有重要的治疗价值。这项建议的目标是建立动物模型，以便准确识别骨组织中的BMSCs，并确定它们对骨骼修复的贡献。

DESCRIPTION (provided by applicant): For many adult skeletal stem cell populations, we lack the ability to identify them in complex tissue environments and determine whether they contribute to the repair of skeletal tissue. The inability to study adult stem cells within their natural environment is a critical barrier that must be overcome in order to advance our understanding of how they contribute to regenerative processes. Here we focus on bone marrow derived mesenchymal stem cells (BMSCs), an adult stem cell population with great therapeutic potential. Genetic approaches in mice can be used that would allow us to identify and fate map BMSCs in bone. Recent developments in our work have identified a new transgenic reporter gene animal model that identifies BMSCs in bone marrow. The objectives of this proposal will continue the characterization of this animal model to confirm our preliminary studies and establish an inducible Cre version that will allow us to fate map this cell population in vivo. Collectively, these animal models will allow us to assay the number of BMSCs present in the bone marrow and determine their contribution over time to skeletal repair. PUBLIC HEALTH RELEVANCE: Bone marrow derived mesenchymal stem cells (BMSCs) are an intensively studied adult stem cell population that retain the ability to differentiate into different skeletal cell types. Therefore, BMSCs have great therapeutic value for skeletal tissue repair. The goal of this proposal focuses on establishing animal models that would allow for the accurate identification of BMSCs in bone tissue and determining their contribution to skeletal repair.