Cardiovascular Cell Therapy Research Network

心血管细胞治疗研究网络

• 批准号: 7209183
• 负责人: James T. Willerson
• 金额: $ 40.06万
• 依托单位: TEXAS HEART INSTITUTE
• 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/7209183
• 关键词: Acute myocardial infarction; Address; Area; Arrhythmia; Attention; Autologous; Bone Marrow; Canis familiaris; Cardiac; Cardiovascular Diseases; Cardiovascular system; Catheters; Cause of Death; Cell Count; Cell Transplants; Cells; Cessation of life; Chronic; Clinical; Clinical Trials; Clinical Trials Cooperative Group; Collaborations; Coronary artery; Data; Development; Dimensions; Dose; Electrocardiogram; Endothelial Cells; Enrollment; Evaluation; Heart Transplantation; Heart failure; Holter Electrocardiography; Image; Inflammation; Injection of therapeutic agent; Ischemia; Life; Magnetic Resonance Imaging; Maps; Measures; Mesenchymal; Modeling; Mononuclear; Motion; Myocardial Ischemia; Myocardial perfusion; Myocardium; N-octanoylglucosylamine; Needles; Numbers; Oxygen Consumption; Patients; Pericardial body location; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Probability; Procedures; Process; Progress Reports; Protocols documentation; Purpose; Quality of life; Research; Research Personnel; Risk; Roentgen Rays; Route; Safety; Sample Size; Site; Smooth Muscle Myocytes; Specific qualifier value; Standards of Weights and Measures; Stem cells; Testing; Therapeutic Studies; Thick; Time; United States National Institutes of Health; Vascular Diseases; Ventricular Ejection Fractions; Walking; Work; abstracting; base; day; effusion; follow-up; hemodynamics; improved; pericardial sac; pre-clinical; preclinical study; precursor cell; single photon emission computed tomography; size; stem cell therapy; tumorigenesis

DESCRIPTION (provided by applicant): Cardiovascular disease is the nation's leading cause of death, claiming a life every 33 seconds, 2600 lives each day, and nearly one million lives each year. For the majority of patients with any type of significantly advanced heart failure, the common, final clinical scenario is of a severely limited quality of life associated with a significant risk of death. The hypothesis behind the proposed projects is that stem cell therapy will benefit patients with varying degrees of heart failure. To date, the cummulative data from our studies and several others demonstrate that stem cell injections appear to be safe and possibly effective in at least some patients with heart failure. Our research consortium has conducted many studies (both pre-clinical and clinical) in this area of research and is currently enrolling patients in an FDA-approved Phase I clinical trial of transendocardial injections of autologous bone marrow-derived mononuclear cells for treatment of patients with advanced heart failure. In this application, we propose 2 potential protocols for the network. Protocol 1 allows us to continue our present trial with a Phase II trial that will also address an important question that remains unanswered: What is the ideal number of cells for transplant? (i.e.: Would 100,000,000 cells be more beneficial than the 30,000,000 we are currently using?) Protocol 2 focuses on the immediate postinfarct period and uses a specific type of stem cell, the Stro bright or mesenchymal precursor cell (MPC). All cells will be injected transendocardially and guided by electromechanical mapping into areas of viable myocardium. Safety of the cell delivery process will be assessed periprocedurely with Holter monitoring, and long-term safety will be assessed clinically for at least 3 years with imaging studies and catheter evaluations. Efficacy will be assessed primarily on the basis of imaging studies (echo, angio, MRI, SPECT, X-ray) and EKG, 24hr Holter monitoring, treadmill with MVO2, and lab work. We have now completed two pre-clinical studies using mesenchymal cell injections in canine models of chronic ischemia and acute myocardial infarction (AMI). Both studies demonstrated that mesenchymal cells injected by the transendocardial route differentiated into smooth muscle cells and endothelial cells, and resulted in increased vascularity and improved cardiac function. If proven safe and effective in FDA-approved clinical trials, these new therapies could extend the lives and improve the quality of life for almost 1 million people each year in the U.S. alone. (End of Abstract)

描述（由申请人提供）： 心血管疾病是全国死亡的主要原因，每33秒，每天有2600次生命，每年寿命近100万。对于大多数具有明显晚期心力衰竭的患者而言，常见的最终临床情况与死亡的重大风险相关的生活质量非常有限。拟议项目背后的假设是干细胞疗法将使心力衰竭程度不同的患者受益。迄今为止，来自我们研究的核能数据以及其他一些数据表明，在至少某些心力衰竭患者中，干细胞注射似乎是安全且可能有效的。我们的研究联盟已经在这一研究领域进行了许多研究（包括临床前和临床），目前正在接受FDA批准的I期临床试验，该试验是对自体骨髓单核细胞的跨心膜注射临床试验，以治疗患有晚期心力衰竭的患者。在此应用程序中，我们为网络提出了2种潜在协议。协议1允许我们通过II期试验继续我们的试验，该试验还将解决一个尚未解决的重要问题：移植的理想细胞数量是多少？ （即：100,000个细胞会比我们目前正在使用的30,000,000个细胞更有益吗？）协议2重点关注立即的后期后期，并使用特定类型的干细胞（Stro stro Bright或间充质前体细胞（MPC））。所有细胞将均可在心脏中心进行注射，并通过机电映射到可行心肌区域的指导。细胞输送过程的安全性将通过螺纹监测来评估腹部，并通过成像研究和导管评估将在临床上进行至少3年的长期安全性。功效将主要根据成像研究（Echo，Angio，MRI，SPECT，X射线），24小时Holter Monumoning，带有MVO2的跑步机和实验室工作来评估功效。现在，我们使用间充质细胞注射术中的慢性缺血模型和急性心肌梗塞（AMI）完成了两项临床前研究。两项研究均表明，由心膜路线注入的间充质细胞分化为平滑肌细胞和内皮细胞，并增加血管性和改善的心脏功能。如果在FDA批准的临床试验中被证明是安全有效的，那么这些新疗法就可以延长生命并改善仅美国每年近100万人的生活质量。 （抽象的结尾）