Repair and Angiogenesis by Stem Cells in Human Heart

人类心脏干细胞的修复和血管生成

基本信息

批准号：
7608830
负责人：
Piero Anversa
金额：
$ 62.33万
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：
2005
资助国家：
美国
起止时间：
2005-08-01 至 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7608830
关键词：
ABCB1 gene Actins Acute Acute Disease Address Adult Affect Age Aging-Related Process Animal Model Animals Antigens Autologous Beds Blood Vessels Blood capillaries Bone Marrow CD34 gene Caliber Cardiac Cardiac Myosins Cardiac Surgery procedures Cardiology Cardiomyopathies Categories Cell Lineage Cell Therapy Cell physiology Cells Characteristics Chronic Chronic Disease Cicatrix Class Clinical Commit Communities Compatible Condition Connexin 43 Contracts Coronary Coronary Vessels Cytoplasmic Protein Defect Desmin Differentiation and Growth Disease Endothelial Cells Epitopes Equilibrium Etiology Event Exercise Exhibits Female Fibroblasts Future Gender Glial Fibrillary Acidic Protein Goals Growth Heart Heart Diseases Heart Hypertrophy Heart failure Hematopoietic Homeostasis Human In Vitro Individual Infarction Injection of therapeutic agent Injury Lead Life MS4A1 gene Malignant Neoplasms Measures Mitotic Modeling Muscle Cells Muscle Fibers Myocardial Myocardial Infarction Myocardium Myogenin Myosin Heavy Chains N-Cadherin Natural regeneration Necrosis Neurons Numbers Organ PECAM1 gene PTPRC gene Pathologic Pathology Patients Phenotype Physiological Population Preparation Primary idiopathic dilated cardiomyopathy Principal Investigator Process Proliferating Property Proteins Proto-Oncogene Protein c-kit Protocols documentation Pump Rate Rattus Recording of previous events Reperfusion Injury Research Research Personnel Research Proposals Resistance Sampling Sea Severities Severity of illness Smooth Muscle Actin Staining Method Smooth Muscle Myocytes Staging Stem cells Structure Surface Antigens Techniques Terminology Testing Therapeutic Thick Tissues Undifferentiated Vascular blood supply Vascular resistance Ventricular Work age effect angiogenesis arteriole base capillary case-based cell growth cell preparation conditioning coronary perfusion illness length improved in vitro Assay in vivo infancy innovation male nestin protein neurofilament protein H novel strategies precursor cell primitive cell progenitor programs promoter receptor reconstitution repaired response self-renewal sex size stem stem cell therapy tissue oxygenation transcription factor von Willebrand Factor

项目摘要

DESCRIPTION (provided by applicant): We have recently identified and characterized a cardiac stem cell (CSC) in the adult human heart. Human CSCs express the stem cell antigens c-kit, MDR1 and Sca-1-like alone or in various combinations. Therefore, one of the major objectives of this application is to determine whether the expression of distinct stem cell epitopes has a functional counterpart resulting in different degrees of CSC growth and differentiation. A number of in vitro assays will be implemented to demonstrate the self-renewal property of these cells and their ability to give rise to committed progenies. This information is crucial for the recognition of the most appropriate autologous CSC preparation to be employed in the treatment of the diseased human heart. To achieve this goal, the effects of the type, duration and severity of the cardiac disease, and the age and gender of the patient on his/her own resident CSC classes will be defined by in vitro protocols to detect the best cell(s) to be employed in each case. To demonstrate whether the criteria introduced in the separations of the CSC categories are valid, the selected CSC populations will be injected in infarcted immunodeficient rats and the extent of myocardial regeneration promoted by each CSC class will be measured. Another important aspect of this research is to determine whether these strategies that may lead to the repair of the acutely damaged heart are equally effective, less effective or completely ineffective in the regeneration of chronic scarred myocardium. Additionally, we will address the issue whether the utilization of CSCs is preferable to the use of cells already committed to the myocyte, endothelial cell and smooth muscle cell lineages or a pool of CSCs and partially differentiated cells provides a greater and faster regenerative response. The committed cells may have a reduced capacity to proliferate but may acquire more rapidly the adult phenotype. Ultimately, CSC/progenitor cell therapy will be established on an individual basis to maximize the efficacy of this novel approach for the management of heart failure in each case.

描述（由申请人提供）：我们最近鉴定并鉴定了成人心脏中的心脏干细胞（CSC）。人类 CSC 单独或以各种组合表达干细胞抗原 c-kit、MDR1 和 Sca-1-like。因此，本申请的主要目标之一是确定不同干细胞表位的表达是否具有功能对应物，从而导致不同程度的CSC生长和分化。将进行许多体外测定，以证明这些细胞的自我更新特性及其产生定型后代的能力。该信息对于识别最适合用于治疗患病人类心脏的自体 CSC 制剂至关重要。为了实现这一目标，将通过体外方案定义心脏病的类型、持续时间和严重程度以及患者的年龄和性别对其自己的常驻 CSC 类别的影响，以检测最佳细胞在每种情况下都将被雇用。为了证明 CSC 类别分离中引入的标准是否有效，将选定的 CSC 群体注射到梗死的免疫缺陷大鼠中，并测量每个 CSC 类别促进的心肌再生程度。这项研究的另一个重要方面是确定这些可能导致急性受损心脏修复的策略对于慢性疤痕心肌的再生是否同样有效、效果较差或完全无效。此外，我们将解决以下问题：使用 CSC 是否优于使用已定型为肌细胞、内皮细胞和平滑肌细胞谱系的细胞，或使用 CSC 和部分分化细胞库提供更大、更快的再生反应。定型细胞的增殖能力可能降低，但可能更快地获得成体表型。最终，CSC/祖细胞疗法将在个体基础上建立，以最大限度地提高这种治疗每个病例心力衰竭的新方法的功效。