Cardiovascular Cell Therapy Research Network

心血管细胞治疗研究网络

• 批准号: 7747946
• 负责人: James T. Willerson
• 金额: $ 39.43万
• 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 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7747946
• 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 Therapy; 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; FDA approved; 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; National Heart, Lung, and Blood Institute; Needles; Oxygen Consumption; Patients; Pericardial body location; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Probability; Procedures; Process; Progress Reports; Protocols documentation; Quality of life; Research; Research Personnel; Risk; Roentgen Rays; Route; Safety; Sample Size; Site; Smooth Muscle Myocytes; Specific qualifier value; Stem cells; Testing; Therapeutic Studies; Thick; Time; United States National Institutes of Health; Vascular Diseases; Ventricular Ejection Fractions; Walking; Work; abstracting; base; effusion; follow-up; hemodynamics; improved; pericardial sac; pre-clinical; preclinical study; precursor cell; single photon emission computed tomography; 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)： 心血管疾病是这个国家的主要死亡原因，每33秒就有一人丧生，每天有2600人死亡，每年有近100万人死亡。对于大多数患有任何类型的严重进展性心力衰竭的患者来说，常见的最终临床情景是严重有限的生活质量与显著的死亡风险相关。这些拟议项目背后的假设是，干细胞疗法将使患有不同程度心力衰竭的患者受益。到目前为止，我们的研究和其他几项研究的累积数据表明，干细胞注射似乎是安全的，至少对一些心力衰竭患者可能有效。我们的研究联盟已经在这一研究领域进行了许多研究(临床前和临床)，目前正在招募患者参加FDA批准的经心内膜内注射自体骨髓来源的单个核细胞治疗晚期心力衰竭患者的I期临床试验。在本申请中，我们为网络提出了两种可能的协议。方案1允许我们继续我们目前的试验，进行第二阶段试验，这也将解决一个仍然没有答案的重要问题：用于移植的理想细胞数量是多少？(即：100,000,000个细胞是否会比我们目前使用的30,000,000个细胞更有益？)方案2侧重于脑梗塞后的即刻阶段，并使用一种特定类型的干细胞，即间质前体细胞(MPC)。所有细胞都将通过心内膜注入，并由机电标测引导进入存活心肌区域。细胞输送过程的安全性将通过Holter监测进行围术期评估，长期安全性将通过成像研究和导管评估进行至少3年的临床评估。疗效的评估将主要基于成像检查(ECHO、Angio、MRI、SPECT、X光)和EKG、24小时Holter监测、MVO2跑步机和实验室工作。我们现在已经完成了两项使用间充质细胞注射在犬慢性缺血和急性心肌梗死(AMI)模型中的临床前研究。这两项研究都表明，经心内膜途径注射的间充质细胞分化为平滑肌细胞和内皮细胞，并导致血管增加和心功能改善。如果FDA批准的临床试验证明这些新疗法安全有效，仅在美国，每年就可以延长近100万人的生命，提高他们的生活质量。 (摘要结束)