HEMATOPOIETIC STEM CELLS IN CARDIOVASCULAR REGENERATIVE MEDICINE

造血干细胞在心血管再生医学中的应用

• 批准号: 7609860
• 负责人: Richard P Visconti
• 金额: $ 17.63万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609860
• 关键词: Ablation; Behavior; Biochemical; Biological; Bone Marrow; Cardiac; Cardiovascular system; Cells; Cessation of life; Cicatrix; Computer Retrieval of Information on Scientific Projects Database; Engraftment; Fibroblasts; Funding; Grant; Hematopoietic stem cells; Homing; Infarction; Institution; Mediating; Messenger RNA; Molecular; Mus; Myocardial Infarction; Rate; Regenerative Medicine; Research; Research Personnel; Resources; Signal Transduction; Source; Tensile Strength; Testing; Tissues; Transplantation; United States National Institutes of Health; Ventricular Remodeling; cell behavior; cytokine; numb protein; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Specific aims  In this project, I will comprehensively evaluate the contribution of HSC-derived cardiac fibroblasts to post-infarction cardiac function and pathological remodeling. Proposed studies will define the molecular and biochemical contribution of these cells to post-infarction scar formation and compare these cell biological behaviors to those of resident cardiac fibroblasts. Proposed experiments will also identify cytokines that elicit homing of HSC-derived cells to the infarct zone and also examine the effects of abrogation of TGFb1-mediated signaling on HSC-derived fibroblasts. The specific aims of this proposal are: a) to test the hypothesis that HSC-derived fibroblasts (HSC-f) participate in post-infarction ventricular remodeling. We will perform comprehensive analysis of expression of post-infarction fibroblast-specific mRNA and protein, numbers and rates of proliferation and death, lineage analysis, and determine the effects of cytokines that influence fibroblast cell behaviors specifically on HSC-fs. b) to test the hypothesis that modulation of HSC-f engraftment into the infarcted cardiac tissue influences post-infarction cardiac function and pathological remodeling. Extensive qualitative and quantitative analysis of cardiac function, tensile strength, and tissue remodeling will be performed to evaluate the effects of myocardial infarction combined with bone marrow mobilization or ablation in clonal HSC-transplanted mice.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 在该项目中，我将全面评估HSC衍生的心脏成纤维细胞对肌功能后心脏功能和病理重塑的贡献。拟议的研究将定义这些细胞对结局后疤痕形成的分子和生化贡献，并将这些细胞生物学行为与常驻心脏成纤维细胞的生物学行为进行比较。提出的实验还将确定将HSC衍生细胞归巢到梗塞区的细胞因子，并研究TGFB1介导的信号传导对HSC衍生的成纤维细胞的废除影响。 该提案的具体目的是： a）检验了HSC衍生的成纤维细胞（HSC-F）参与进攻后心室重塑的假设。我们将对成纤维后成纤维细胞特异性mRNA和蛋白质的表达进行全面分析，增殖和死亡的数量和速率，谱系分析，并确定特异性影响成纤维细胞行为对HSC-FS的细胞因子的影响。 b）检验以下假设：调节HSC-F植入梗塞心脏组织会影响进攻后心脏功能和病理重塑。将进行心脏功能，拉伸强度和组织重塑的广泛定性和定量分析，以评估心肌梗塞的影响以及骨髓动员或在克隆HSC转移的小鼠中的骨髓动员或消融。