Cell Based Therapy for Non-Ischemic Dilated Cardiomyopathy

非缺血性扩张型心肌病的细胞疗法

基本信息

批准号：
8448599
负责人：
Joshua M Hare
金额：
$ 65.07万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-03-23 至 2019-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8448599
关键词：
Accounting Address Advanced Development Autologous Award Biology Biopsy Bone Marrow Cardiac Cardiomyopathies Cardiovascular system Catheters Cell Proliferation Cell Therapy Cell surface Cells Cellular Morphology Cessation of life Cicatrix Clinical Clinical Research Clinical Trials Clinical Trials Design Coculture Techniques Combined Modality Therapy Congestive Heart Failure Data Databases Diamond Dilated Cardiomyopathy Disease Dose Drug Formulations EFRAC Enrollment Experimental Models Family suidae Fibrosis Foundations Functional disorder Growth Health Heart Heart Transplantation Heart failure Human Image In Vitro Individual Injection of therapeutic agent Institutes Investigation Lead Left Ventricular Function Measures Mesenchymal Stem Cells Methods Modeling Myocardial Ischemia N-octanoylglucosylamine National Heart, Lung, and Blood Institute Outcome Patient Selection Patients Perfusion Phase Phenotype Preparation Primary idiopathic dilated cardiomyopathy Program Development Property Randomized Randomized Clinical Trials Relative (related person)Role Safety Solid Specialized Center Stem cells System Testing Therapeutic Tissues Treatment Efficacy Ventricular Remodeling Work base cell type clinically relevant design disability experience heart function improved injured innovation insight novel novel strategies novel therapeutic intervention novel therapeutics patient population pre-clinical programs research study safety testing skills stem cell therapy sudden cardiac death

项目摘要

DESCRIPTION (provided by applicant): This application to participate in the CCTRN proposes clinical research skills development program and phase l/ll randomized clinical trial evaluating the safety and efficacy of novel cell-based therapeutic strategy for idiopathic dilated cardiomyopathy (IDCM), a leading cause of heart failure (HF), death and disability. This trial will have major impact in the field of cell-baed therapy for IDCM as new approach to produce durable and sustainable improvements in heart function and to cause reverse remodeling. This trial is built on solid foundation of extensive preclinical and clinical work demonstrating that: 1) intramyocardial cell delivery can be safely and effectively performed using catheter based system in HF patients, and 2) bone marrow-derived mesenchymal stem cells (MSCs) are well tolerated, engraft in injured tissues, and stimulate endogenous cardiac stem cell (CSC) proliferation and differentiation. Accordingly, the hypothesis to be tested is that combining CSCs and MSCs will enhance the therapeutic efficacy relative to use of MSCs alone. The mechanism of action at phenotypic level will be assessed using cardiac MRI to measure regional and global LV function, tissue fibrosis, and tissue perfusion. Post-hoc analysis will be performed to test the hypothesis that in vitro assessments of cell morphology, cell surface markers, and cell colony growth potential may predict ability of individual patient's cells to improve cardiac measures. Cellular mechanisms of action of MSC therapy will be assessed by measuring capacity for endogenous CSC proliferation and differentiation. Endomyocardial biopsies will be obtained and tested for their capacity to yield endogenous CSCs. Our group has extensive experience with catheter delivery of MSCs in patients with ischemic and non-ischemic HF. Accordingly, this study is timely, warranted, and may have major health impact by addressing unmet need in IDCM patients. This program will break new ground in field by testing novel therapeutic approach, combining two cell types that together have synergistic properties demonstrated biologically. Together, these aims will advance our understanding of cell-based therapy for IDCM, with specific emphasis placed upon parameters of patient selection, cell delivery strategies, and the impact of novel cell formulations.

描述（由申请人提供）：该参与CCTRN的应用提出了临床研究技能开发计划和LL/LL随机临床试验，该试验评估了新型基于细胞的特发性膨胀心肌病（IDCM）的安全性和功效，这是心力衰竭（HF），死亡和残疾的主要原因。该试验将对IDCM的细胞疗法领域产生重大影响，作为产生持久和可持续改善心脏功能并引起反向重塑的新方法。该试验建立在广泛的临床前和临床工作的坚实基础上，表明：1）心脏内心脏细胞的递送可以在HF患者中使用基于导管的系统安全有效地进行，并且2）骨髓衍生的间质干细胞（MSC）良好的耐受性，在受伤的组织中易于耐受性，并刺激内源性干细胞（CSSC）。因此，要检验的假设是，相对于单独使用MSC，将CSC和MSC结合起来将增强治疗功效。将使用心脏MRI评估表型水平的作用机理，以测量区域和全球LV功能，组织纤维化和组织灌注。将进行事后分析，以检验以下假设：细胞形态，细胞表面标记和细胞菌落生长潜力的体外评估可能可以预测单个患者细胞改善心脏测量的能力。 MSC治疗作用的细胞机制将通过测量内源性CSC增殖和分化能力来评估。将获得内膜活检并测试其产生内源性CSC的能力。我们的小组在缺血性和非缺血性HF患者的MSC导管递送方面具有丰富的经验。因此，这项研究是及时的，有必要的，并且可能通过满足IDCM患者未满足的需求而产生重大健康影响。该程序将通过测试新型的治疗方法来打破现场的新基础，并将两种细胞类型结合在一起，这些细胞类型在生物学上证明了协同特性。总之，这些目标将提高我们对基于细胞的IDCM疗法的理解，并特别强调患者选择，细胞递送策略以及新型细胞配方的影响。