HEMATOPOIETIC STEM CELLS IN CARDIOVASCULAR REGENERATIVE MEDICINE

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 具体目标  在本项目中，我将全面评估HSC来源的心脏成纤维细胞对梗死后心脏功能和病理重构的贡献。拟议的研究将确定这些细胞对梗死后瘢痕形成的分子和生化贡献，并将这些细胞的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引起HSC衍生的细胞归巢到梗死区的细胞因子，并且还检查废除TGF β 1介导的信号传导对HSC衍生的成纤维细胞的影响。 这项建议的具体目标是： a）检验HSC来源的成纤维细胞（HSC-f）参与梗死后心室重构的假设。我们将对梗死后成纤维细胞特异性mRNA和蛋白的表达、增殖和死亡的数量和速率、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对HSC-fs的特异性影响。 B）检验HSC-f移植入梗塞心脏组织的调节影响梗塞后心脏功能和病理性重塑的假设。将对心脏功能、抗张强度和组织重塑进行广泛的定性和定量分析，以评价心肌梗死联合骨髓动员或消融对克隆HSC移植小鼠的影响。

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.