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: 7959858
• 负责人: Richard P Visconti
• 金额: $ 20.52万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959858
• 关键词: Acute; Behavior; Biochemical; Biological; Bone Marrow; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cells; Cessation of life; Chronic; Cicatrix; Collagen Type I; Computer Retrieval of Information on Scientific Projects Database; DDR2 gene; Engraftment; Fibroblasts; Funding; Grant; Hematopoietic stem cells; Home environment; Infarction; Institution; Messenger RNA; Molecular; Mus; Myocardial Infarction; Myocardium; Population; Proteins; Regenerative Medicine; Research; Research Personnel; Resources; Signal Transduction; Source; Tensile Strength; Testing; Tissues; Transplantation; United States National Institutes of Health; Ventricular Remodeling; Wild Type Mouse; base; in vivo; periostin; population based; protein expression; research study; response

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. Our preliminary studies, using lineage-marked (EGFP+) bone marrow, demonstrate that there is hematopoietic stem cell contribution to the cardiac fibroblast population, based on our findings that a sub-population of HSC-derived cells express DDR2 and synthesize collagen type I in the infarcted myocardium. These HSC-derived cells, which densely populate the damaged myocardium, could possibly be used to modulate the degree of pathological remodeling in the post-infarction myocardium. Proposed studies will define the molecular and biochemical contribution of HSC-derived cardiac fibroblasts to post-infarction scar formation and cardiac function, and compare these cell biological behaviors to those of resident cardiac fibroblasts. Proposed experiments will also examine the effects of modulation of numbers of HSC-derived cells that engraft into the myocardium in response to infarction as well as the effects of modulation of periostin signaling on the fibroblastic differentiation of HSC-derived cells that home to the infarct zone. There are three aims: 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, rates of proliferation and death, and lineage analysis of 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, analysis of cardiac function, tensile strength, and tissue remodeling will be performed to evaluate the effects of myocardial infarction combined with modulation of bone marrow mobilization in HSC-transplanted mice. c) to test the hypothesis that the matricellular protein periostin is an active effector of fibroblastic differentiation by HSC-derived cells that engraft into the post-infarction scar. Fibroblast-specific mRNA and protein expression, in vivo fibrogenic response and cardiac functional analyses will be performed in wild-type mice engrafted with PN-/- bone marrow HSCs (vs. wild type HSCs) and subjected to MI to determine the effects of modulation of PN expression on acute and chronic pathological remodeling of the myocardium.

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。 我们使用谱系标记（EGFP+）骨髓的初步研究表明，基于我们的发现，基于我们的发现，HSC衍生细胞的亚构造表现出DDR2和合成I型I型I型肌con骨，对心脏成纤维细胞群体有造血性干细胞的贡献。这些HSC衍生的细胞密集地填充了受损的心肌，可用于调节输入后心肌中的病理重塑程度。 拟议的研究将定义HSC衍生的心脏成纤维细胞对界面后疤痕形成和心脏功能的分子和生化作用，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。提出的实验还将检查响应梗塞的HSC衍生细胞数量调节的影响，以及骨膜蛋白信号传导调节对HSC衍生细胞的成纤维细胞分化的影响，这些细胞的成纤维细胞分化，这些细胞源于梗塞区。有三个目标： a）为了测试HSC衍生的成纤维细胞（HSC-F）参与感染后心室重塑的假设，我们将对侵蚀后成纤维细胞特异性mRNA和蛋白质的表达进行全面分析，增殖和死亡率和死亡的速率以及HSC-FS的谱系分析。 b) to test the hypothesis that modulation of HSC-f engraftment into the infarcted cardiac tissue influences post-infarction cardiac function and pathological remodeling, analysis of cardiac function, tensile strength, and tissue remodeling will be performed to evaluate the effects of myocardial infarction combined with modulation of bone marrow mobilization in HSC-transplanted mice. c）测试了植物蛋白骨膜素是由HSC衍生细胞的成纤维细胞分化的活性效应的假设，这些细胞植入了输入后疤痕中。成纤维母细胞特异性的mRNA和蛋白质表达，体内纤维化反应和心脏功能分析将在植入PN - / - 骨髓HSC（相对于野生型HSC）的野生型小鼠中进行，并受到MI的影响，并通过MI进行MI，以确定PN表达对急性和循环改速的PN表达影响。