Cell Based Therapy for Non-Ischemic Dilated Cardiomyopathy

非缺血性扩张型心肌病的细胞疗法

• 批准号: 8288406
• 负责人: Joshua M Hare
• 金额: $ 71.55万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 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/8288406
• 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

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）： 本次参与 CCTRN 的申请提出了临床研究技能开发计划和 l/ll 期随机临床试验，评估新型细胞治疗策略治疗特发性扩张型心肌病 (IDCM) 的安全性和有效性，特发性扩张型心肌病是心力衰竭 (HF) 的主要原因、死亡和残疾。该试验将在 IDCM 细胞疗法领域产生重大影响，作为产生持久和可持续的心脏功能改善并引起逆转重塑的新方法。该试验建立在广泛的临床前和临床工作的坚实基础上，证明：1）可以使用基于导管的系统在心力衰竭患者中安全有效地进行心肌内细胞输送，2）骨髓来源的间充质干细胞（MSC）良好耐受，植入受伤组织，并刺激内源性心脏干细胞（CSC）增殖和分化。因此，要测试的假设是，相对于单独使用 MSC，组合 CSC 和 MSC 将增强治疗功效。将使用心脏 MRI 来评估表型水平的作用机制，以测量局部和整体左心室功能、组织纤维化和组织灌注。将进行事后分析来检验以下假设：细胞形态、细胞表面标记物和细胞集落生长潜力的体外评估可以预测个体患者细胞改善心脏测量的能力。将通过测量内源性 CSC 增殖和分化的能力来评估 MSC 治疗的细胞作用机制。将获得心内膜心肌活检并测试其产生内源性 CSC 的能力。我们的团队在缺血性和非缺血性心力衰竭患者的间充质干细胞导管输送方面拥有丰富的经验。因此，这项研究是及时的、有根据的，并且可能通过解决 IDCM 患者未满足的需求而产生重大的健康影响。该计划将通过测试新的治疗方法，将两种具有生物学上证明的协同特性的细胞类型结合起来，在该领域开辟新天地。总之，这些目标将增进我们对 IDCM 细胞疗法的理解，特别强调患者选择参数、细胞递送策略和新型细胞制剂的影响。