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

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)： 心力衰竭是美国医院入院的最常见原因，特别是在医疗保险人群中。大多数心力衰竭患者的左心功能不佳，其中60%-70%是由于慢性缺血性冠状动脉疾病。其余患者由于各种其他原因而出现心衰，包括特发性和病毒性心肌病，并被归类为扩张型非缺血性心肌病。 干细胞(内皮细胞、间充质细胞、骨骼细胞或来自骨髓)直接注入心肌或输送到冠脉循环，可以改善慢性缺血性心肌病或急性心肌梗死后的心功能。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效果的确切机制仍不清楚。我们和其他人已经证明，心肌梗死后内皮祖细胞(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，这有助于提高心肌存活率。我们推测，丰富的、混合的干细胞群体可能比单一细胞类型更具优势。我们的研究还表明，在全身移植过程中，干细胞和血管壁之间的积极相互作用对于有效移植的发生是必要的。 这项建议描述了两种使用骨髓来源的细胞治疗左心功能不全的临床方案。第一项研究将检验这样一种假设：与新鲜采集的骨髓细胞相比，扩增骨髓细胞以产生高水平的内皮和间充质祖细胞将在心脏功能方面产生更大的改善。第二项研究将探讨细胞疗法在扩张型非缺血性心肌病中的作用，并验证腺苷预处理将增强细胞归巢的假说，从而增强细胞疗法的有益效果。为了促进未来的研究，临床研究技能开发核心将培训心脏细胞疗法方面的新临床研究人员。 这两个临床方案将确定不同细胞制剂的有效性，以及调节干细胞在靶组织中植入以恢复心功能的作用，为采用可行、易用的策略获取骨髓来源细胞的愈合特性开辟了道路。(摘要结束)