Defining mesenchymal progenitor cell subpopulations

定义间充质祖细胞亚群

• 批准号: 8010952
• 负责人: CATHERINE H Hackett
• 金额: $ 6.1万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8010952
• 关键词: Adipose tissue; Adult; Animals; Antibodies; Arthritis; Aspirate substance; Biochemical; Bone Diseases; Bone Marrow; Cartilage; Cell Count; Cell Surface Proteins; Cell physiology; Cells; Characteristics; Classification; Clinical; Clone Cells; Colony-forming units; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Foundations; Future; Gene Expression; Goals; Harvest; Healed; Health; Histocompatibility Antigens Class II; Histocompatibility Testing; Immunohistochemistry; In Vitro; Intention; Joint repair; Knowledge; MHC Class II Genes; Measures; Membrane Proteins; Mesenchymal Stem Cells; Molecular; Muscle; Organ Transplantation; Outcome; Population; Research; SCID Mice; Source; Stem Cell Research; Stem cells; Techniques; Telomerase; Teratoma; Therapeutic Effect; Tissue Engineering; Tissues; Wound Healing; adult stem cell; base; bone; clinical application; expectation; healing; immunogenic; improved; in vitro Assay; in vivo; insight; knowledge base; molecular marker; mouse model; novel strategies; progenitor; programs; research study; restoration; stem cell biology

DESCRIPTION (provided by applicant: The broad objectives of this study are to identify the optimal adult-derived tissue source (bone marrow, muscle, or adipose tissue) for isolation of mesenchymal progenitor cells capable of differentiating into cartilage or bone. Successful completion of the studies outlined in this proposal will provide a strong foundation for our long term goal of refining present strategies for improved clinical outcome of stem cell enhanced restoration of bone or cartilage. The hypothesis of this proposal is that a progenitor cell subpopulation with a capacity to preferentially differentiate into cartilage or bone can be identified and isolated from other cell subpopulations derived from bone marrow aspirate, muscle, or adipose tissue. As a first step towards reaching our long-term objective we will define unique features of subpopulations of mesenchymal progenitor cells (MPC)s derived from adult-derived bone marrow aspirate, muscle, and adipose tissues. We will then quantify the number of stem cells that can be obtained from each tissue, and finally, we will determine which tissue(s) provides the optimal MPC source for differentiation into cartilage or bone. To achieve these goals, will use single cell cloning, gene expression levels with quantitative RT PCR, flow cytometric analyses of several cell surface protein markers, and immunohistochemical techniques. Expanding our knowledge of MPC subpopulations is an important step toward understanding stem cell physiology and is essential for critical assessment of MPC-based grafting procedures. The expectation is that completion of the studies outlined in this proposal will provide important insight into the identification and isolation of MPC subpopulations. A more precise understanding of the heterogenous population of MPC obtained from adult tissues should improve differentiation of MPCs into cartilage and bone. We anticipate that these findings will have a major impact on the clinical use of MPCs in targeted tissue repair applications. The research in this proposal is important for improving the health of millions afflicted with arthritis or bone diseases. Our studies will expand the present knowledge base concerning adult tissue-derived stem cell biology with a specific focus on the clinical application of stem cells for repair of joints and bones.

描述（由申请人提供：本研究的广泛目的是确定最佳的成人衍生的组织（骨髓，肌肉或脂肪组织），用于隔离间质祖细胞，能够分化为软骨或骨骼。成功完成该建议中的研究概述了我们的长期临床策略的强大基础，以提高骨骼的临时性基础。 该提议的假设是，可以鉴定出具有优先分化为软骨或骨骼的能力的祖细胞亚群，并与来自骨髓骨髓抽吸物，肌肉或脂肪组织得出的其他细胞亚群。作为达到长期目标的第一步，我们将定义从成人衍生的骨髓抽吸物，肌肉和脂肪组织衍生的间充质祖细胞（MPC）的独特特征。然后，我们将量化可以从每个组织获得的干细胞数量，最后，我们将确定哪种组织提供了最佳的MPC来源，以分化为软骨或骨骼。为了实现这些目标，将使用单细胞克隆，具有定量RT PCR的基因表达水平，几个细胞表面蛋白标记的流式细胞仪分析以及免疫组织化学技术。扩展我们对MPC亚群的了解是了解干细胞生理的重要一步，对于基于MPC的嫁接程序的重要评估至关重要。 期望本提案中概述的研究的完成将为MPC亚群的识别和隔离提供重要的见解。对从成人组织获得的MPC的异质种群的更精确理解应改善MPC分化为软骨和骨骼。我们预计这些发现将对目标组织修复应用中MPC的临床使用产生重大影响。 该提案中的研究对于改善患有关节炎或骨骼疾病的数百万的健康很重要。我们的研究将扩大有关成年组织衍生的干细胞生物学的当前知识库，特别关注干细胞在关节和骨骼上修复干细胞的临床应用。