HEMATOPOIETIC STEM CELLS IN CARDIOVASCULAR REGENERATIVE MEDICINE

这个子项目是众多研究子项目之一

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.