Cardiac Stem Cells and Angiomyogenesis

心脏干细胞和血管肌生成

基本信息

批准号：
8218441
负责人：
JAN KAJSTURA
金额：
$ 42.27万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-12-02 至 2016-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8218441
关键词：
Adult Age Age-Months Aging Anemia Animals Attenuated Biological Preservation Birth Cardiac Cardiac Myocytes Cell Lineage Cells Chromatids Clonality Commit Contracts Coronary Vessels Cytoplasmic Protein DNA DNA biosynthesis Data Daughter Development Differentiation and Growth Disease Documentation Embryo Embryonic Heart Endothelial Cells Environmental Risk Factor Goals Growth Heart Heart Diseases Heart failure Human Hypertrophy In Vitro Individual Inherited Laboratories Lead Life Life Cycle Stages Longevity Methodology Modeling Mothers Mus Muscle Cells Myocardial Myocardium Myopathy Organ Oxidative Stress Phenotype Process Proliferating Property Proto-Oncogene Protein c-kit Protocols documentation Replication Error Research Role Sister Smooth Muscle Myocytes Stem cells Undifferentiated Vascular Endothelial Cell Viral cardiogenesis cell growth daughter cell fetal in vivo loss of function postnatal prenatal prevent progenitor segregation self-renewal senescence stem cell division theories transcription factor vasculogenesis

项目摘要

DESCRIPTION (provided by applicant): The recognition that a pool of cardiac stem cells (CSCs) is present in the adult myocardium poses the question whether CSCs are responsible for cardiomyogenesis in the embryonic, fetal and postnatal heart, regulate myocyte renewal in the adult organ and condition myocardial aging. Stem cell renewal occurs by symmetric division, which generates two daughter stem cells, or by asymmetric division, which generates one daughter cell that is identical to the mother cell and a second daughter cell which has a separate fate. This notion of stem cell growth has recently been perturbed by the resurrection of an old theory, suggesting that stem cells are capable of cosegregating the old original template DNA strands in consecutive divisions so that the daughter cell that inherits the old DNA retains stem cell features while the daughter cell that acquires the new DNA enters the transit amplifying pool. If this hypothesis is correct, the number of mother stem cells may be genetically determined sometime early in life and cannot be expanded thereafter. Conversely, this class of "true" stem cells may decrease dramatically as a function of age and loss of CSCs may be a critical determinant of the development of the aging myopathy. Protection of the old DNA during stem cell division cannot prevent the consequences of oxidative stress and environmental factors commonly present with the course of life and myocardial aging, independently from disease processes. Excessive growth demands on CSCs may lead to their depletion and, as a consequence, to accumulation of senescent, poorly contracting, hypertrophied cardiomyocytes. Conversely, preservation of the pool of CSCs carrying the mother DNA may delay the manifestations of the senescent cardiac phenotype. Thus, the long-term objective of this application is to establish the role of endogenous CSCs in the development of the heart prenatally and postnatally, and their function in the fully mature organ and in the initiation and progression of the aging myopathy. PUBLIC HEALTH RELEVANCE: This research is directed to the documentation whether the entire lifespan of the heart from embryonic, fetal and postnatal development to adulthood and aging is regulated by the growth and differentiation of resident cardiac stem cells. Additionally, the possibility is raised that the loss of a pool of true stem cells that is genetically determined may condition myocardial aging and heart failure.

描述（由申请人提供）：成人心肌中存在心脏干细胞（CSC）库（CSC）的认识提出了一个问题，该问题是否负责胚胎，胎儿和产后心脏中的心肌生成，调节成人器官和状况的心肌和心肌老化的心肌细胞更新。干细胞更新是由对称分裂发生的，它会产生两个子干细胞，或通过非对称分裂产生与母细胞相同的子细胞和一个具有单独命运的儿子细胞。最近，这种旧理论的复活使干细胞生长的概念受到了干扰，这表明干细胞能够连续分隔中旧的原始模板DNA链，以便继承旧DNA的子细胞保留干细胞的子细胞，而女子细胞则获得了新的DNA，从而获得了新的DNA进入交通恢复池。如果该假设是正确的，则可以在生命早期的某个时候确定母细胞的数量，此后不能扩展。相反，这类“真实”干细胞可能会随着年龄的变化而大大减少，而CSC的损失可能是衰老肌病发展的关键决定因素。干细胞分裂期间旧DNA的保护无法阻止氧化应激和环境因素的后果，而环境因素通常与疾病过程无关。 CSC的过度增长需求可能导致它们的枯竭，因此，积累了衰老，收缩不良，肥厚的心肌细胞。相反，携带母体DNA的CSC池的保存可能会延迟衰老心脏表型的表现。因此，该应用的长期目标是在产前和产后建立内源性CSC在心脏发展中的作用，及其在完全成熟器官以及衰老肌病的起始和进展中的功能。公共卫生相关性：这项研究针对文档，是否由胚胎，胎儿和产后发展到成年和衰老的整个心脏寿命受到居民心脏干细胞的生长和区分的调节。此外，可能性的可能性是，在遗传上确定的真实干细胞的损失可能调节心肌衰老和心力衰竭。