HEMATOPOIETIC STEM CELLS IN CARDIOVASCULAR REGENERATIVE MEDICINE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本课题旨在全面评价肝星状细胞来源的心脏成纤维细胞在心肌梗死后心功能和病理重塑中的作用。拟议的研究将确定这些细胞在梗死后瘢痕形成中的分子和生化作用，并将这些细胞的生物学行为与心脏成纤维细胞的生物学行为进行比较。拟议的实验还将确定诱导HSC来源的细胞归巢到梗死区的细胞因子，并检测取消TGFb1介导的信号对HSC来源的成纤维细胞的影响。 这项建议的具体目标是： A)验证HSC来源的成纤维细胞(HSC-f)参与心肌梗死后心室重构的假说。我们将对梗死后成纤维细胞特异的mRNA和蛋白的表达、增殖和死亡的数量和比率、谱系分析进行综合分析，并确定影响成纤维细胞行为的细胞因子在HSC-f上的作用。 B)验证HSC-f移植到梗死心肌组织的调节影响梗死后心功能和病理重塑的假设。对心功能、抗张强度和组织重塑进行广泛的定性和定量分析，以评估克隆性HSC移植小鼠心肌梗死合并骨髓动员或消融的效果。

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.