Cell Therapy for Improving Cardiac Function

改善心脏功能的细胞疗法

• 批准号: 7212901
• 负责人: Douglas E Vaughan
• 金额: $ 55.41万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7212901
• 关键词: Acute myocardial infarction; Address; Adenosine; Admission activity; Aftercare; Age; Beds; Blood Vessels; Bone Marrow; Bone Marrow Cells; Cardiac; Cardiomyopathies; Catheters; Cell Adhesion; Cell Therapy; Cell-Matrix Junction; Cells; Cessation of life; Chronic; Clinical; Clinical Investigator; Clinical Protocols; Clinical Research; Clinical Research Protocols; Congestive Heart Failure; Consent; Coronary; Coronary Artery Bypass; Coronary Circulation; Coronary heart disease; Coronary sinus structure; Development; Diagnosis; Dilated Cardiomyopathy; Disease; EFRAC; Engraftment; Enrollment; Experimental Models; Ficoll; Fostering; Future; Harvest; Healed; Heart; Heart Diseases; Heart Transplantation; Heart failure; Homing; Hospitalization; Hospitals; Infarction; Infusion procedures; Left Ventricular Dysfunction; Left Ventricular Ejection Fraction; Left Ventricular Function; Magnetic Resonance Imaging; Mediating; Medical; Medicare; Mesenchymal; Mesenchymal Stem Cells; Mononuclear; Muscle Cells; Myocardial; Myocardial Infarction; Myocardium; Natural regeneration; Numbers; Operative Surgical Procedures; Organ; Patients; Placebos; Population; Preparation; Prevention; Procedures; Process; Property; Randomized; Reporting; Research; Research Personnel; Residual state; Role; Skeletal system; Staging; Standards of Weights and Measures; Stem cells; Structure; Testing; Time; Tissues; Training; Treatment Efficacy; United States; Upper arm; Ventricular Function; Viral; Week; Work; Wound Healing; abstracting; angiogenesis; cell preparation; cell type; cytokine; day; design; experience; healing; heart function; improved; indexing; paracrine; placebo controlled study; prevent; programs; prospective; skills; Acute myocardial infarction; Address; Adenosine; Admission activity; Aftercare; Age; Beds; Blood Vessels; Bone Marrow; Bone Marrow Cells; Cardiac; Cardiomyopathies; Catheters; Cell Adhesion; Cell Therapy; Cell-Matrix Junction; Cells; Cessation of life; Chronic; Clinical; Clinical Investigator; Clinical Protocols; Clinical Research; Clinical Research Protocols; Congestive Heart Failure; Consent; Coronary; Coronary Artery Bypass; Coronary Circulation; Coronary heart disease; Coronary sinus structure; Development; Diagnosis; Dilated Cardiomyopathy; Disease; EFRAC; Engraftment; Enrollment; Experimental Models; Ficoll; Fostering; Future; Harvest; Healed; Heart; Heart Diseases; Heart Transplantation; Heart failure; Homing; Hospitalization; Hospitals; Infarction; Infusion procedures; Left Ventricular Dysfunction; Left Ventricular Ejection Fraction; Left Ventricular Function; Magnetic Resonance Imaging; Mediating; Medical; Medicare; Mesenchymal; Mesenchymal Stem Cells; Mononuclear; Muscle Cells; Myocardial; Myocardial Infarction; Myocardium; Natural regeneration; Numbers; Operative Surgical Procedures; Organ; Patients; Placebos; Population; Preparation; Prevention; Procedures; Process; Property; Randomized; Reporting; Research; Research Personnel; Residual state; Role; Skeletal system; Staging; Standards of Weights and Measures; Stem cells; Structure; Testing; Time; Tissues; Training; Treatment Efficacy; United States; Upper arm; Ventricular Function; Viral; Week; Work; Wound Healing; abstracting; angiogenesis; cell preparation; cell type; cytokine; day; design; experience; healing; heart function; improved; indexing; paracrine; placebo controlled study; prevent; programs; prospective; skills

DESCRIPTION (provided by applicant): Heart Failure is the most common reason for admission to hospitals in the United States, especially in the Medicare population. A majority of patients with HF have poor left ventricular function, with 60-70% due to chronic ischemic coronary disease. The remainder of patients experience HF due to a variety of other causes, including idiopathic and viral cardiomyopathies, and are classified as dilated non-ischemic cardiomyopathies. Stem cells (endothelial, mesenchymal, skeletal or from bone marrow), injected directly into the myocardium or delivered to the coronary circulation, can improve cardiac function in chronic ischemic cardiomyopathy or following an acute myocardial infarction. While there is evidence that cell therapy can improve cardiac function, the exact mechanisms through which cell therapy exerts beneficial effects remain unclear. We and others have demonstrated that the cardioprotective effects of endothelial progenitor cells (EPCs) following myocardial infarction are mediated, in part, by multiple cytokines secreted by stem cells, which can favorably enhance myocardial survival. We postulate that an enriched, mixed, stem cell population may offer an advantage over a single cell type. It is also evident from our studies that active interaction between stem cells and the vascular wall during systemic delivery is necessary for efficient grafting to occur. This proposal describes two clinical protocols to use bone marrow-derived cells for the treatment of left ventricular dysfunction. The first will test the hypothesis that expansion of bone marrow cells to yield high levels of endothelial and mesenchymal progenitor cells will produce a greater improvement in cardiac function compared to freshly harvested bone marrow cells. The second will investigate the role of cell therapy in dilated non-ischemic cardiomyopathy and test the hypothesis that adenosine pretreatment will enhance cell homing potentiating the beneficial effects of cell therapy. To foster future research, a Clinical Research Skills Development Core will train new clinical investigators in cardiac cell-therapy. The two clinical protocols will determine the efficacy of different cell preparations and the role of modulating stem cell engraftment in target tissue to restore ventricular function opening the way for feasible, easily applied strategies to capture the healing properties of bone marrow-derived cells. (End of Abstract)

描述（由申请人提供）： 心力衰竭是美国，尤其是在医疗保险人群中入院的最常见原因。大多数HF患者的左心室功能较差，由于慢性缺血性冠状动脉疾病，其60-70％。由于其他多种原因，包括特发性和病毒性心肌病，其余患者经历了HF，并被归类为扩张的非缺血性心肌病。 干细胞（内皮，间充质，骨骼或骨髓）直接注射到心肌或递送到冠状动脉循环中，可以改善慢性缺血性心肌病的心脏功能或急性心肌梗塞后的心脏功能。虽然有证据表明细胞疗法可以改善心脏功能，但细胞疗法发挥有益作用的确切机制尚不清楚。我们和其他人已经证明，心肌梗塞后内皮祖细胞（EPC）的心脏保护作用部分是由干细胞分泌的多种细胞因子介导的，从而可以很好地增强心肌生存。我们假设，富集，混合的干细胞种群可能比单个细胞类型具有优势。从我们的研究中也可以明显看出，在全身传递过程中，干细胞与血管壁之间的主动相互作用对于有效的接枝是必要的。 该建议描述了使用骨髓衍生细胞治疗左心室功能障碍的两种临床方案。第一个将检验以下假设：与新鲜收获的骨髓细胞相比，与新的内皮细胞和间充质祖细胞产生高水平的内皮和间质祖细胞的扩张将产生更大的改善。第二个将研究细胞疗法在膨胀的非缺血性心肌病中的作用，并检验腺苷预处理的假设将增强细胞归纳增强细胞疗法的有益作用。为了促进未来的研究，临床研究技能发展核心将在心脏细胞治疗中培训新的临床研究者。 这两种临床方案将确定不同细胞制剂的功效以及调节靶组织中干细胞植入的作用，以恢复心室功能为可行，易于应用的策略开辟了道路，以捕获骨髓衍生细胞的愈合特性。 （抽象的结尾）