Cellular Cardiomyoplasty for Acute and Chronic Ischemic

急性和慢性缺血性细胞心肌成形术

• 批准号: 7126373
• 负责人: EDUARDO MARBAN
• 金额: $ 235万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7126373
• 关键词: acute disease /disorder; cardiogenesis; chronic disease /disorder; clinical research; hematopoietic tissue transplantation; myocardial infarction; stem cell transplantation

DESCRIPTION (provided by applicant): This Specialized Center for Cell Therapeutics proposal aims to develop cellular cardiomyoplasty for the treatment of ischemic heart disease, both post-myocardial infarction left ventricular dysfunction as well as chronic ischemic cardiomyopathy. Currently, there is extraordinary enthusiasm for the development of cell-based therapies for diseases resulting from ischemic damage to the myocardium. Rapid advances have been made in animal models and preliminary clinical trials suggest that cardiac function in acute and chronic heart disease may be improved. Currently the bone marrow remains as a highly promising source of precursor cells for cardiac repair. Our group has been involved in collaboration with Osiris Therapeutics in developing bone-marrow derived mesenchymal stem cells (MSCs) for the use of cellular cardiomyoplasty, and the results of this work have led to the upcoming initiation of the first clinical trial of this cell type for humans with myocardial infarction. In addition, cardiac stem cells have now been identified that can be amplified in culture as a source of cells for cardiac repair. This proposal is based upon extensive basic and preclinical data supporting the value of both MSCs and cardiac stem cells (CSCs) for cellular cardiomyoplasty. A major strength of the approach is our ability to prepare adequate numbers of cardiac stem cells from biopsy specimens for use in therapeutic applications. The approach is three-fold with substantial synergies. First, in Project 1 MSCs will be explored in clinical trials of humans with ischemic cardiomyopathy based on an existing extensive pre-clinical database, an established safety record in humans, and already-planned clinical trials for patients with acute myocardial infarction. Second, we will concurrently in Project 2 continue characterizing CSCs obtained from humans and perform relevant preclinical experiments. Finally, based on the substantial experience obtained in Project 1 with delivery techniques and efficacy monitoring developed, and the cellular methods perfected in Project 2, we will perform clinical trials of CSCs in Project 3. Together, this program will have the capability of performing highly-relevant and clinically informative trials that will be guided and refined by the latest advances in basic cell biology.

描述（由申请人提供）： 该细胞治疗专业中心的提案旨在开发用于治疗缺血性心脏病的细胞心肌成形术，包括心肌梗死后左心室功能障碍以及慢性缺血性心肌病。目前，对于开发用于由心肌缺血性损伤引起的疾病的基于细胞的疗法有着非凡的热情。在动物模型方面取得了快速进展，初步临床试验表明，急性和慢性心脏病的心脏功能可能会得到改善。目前，骨髓仍然是心脏修复的前体细胞的一个非常有前途的来源。我们的团队一直在与Osiris Therapeutics合作开发用于细胞心肌成形术的骨髓间充质干细胞（MSC），这项工作的结果导致了即将开始的第一个临床试验这种细胞类型的人类心肌梗死。此外，心脏干细胞现在已经被鉴定为可以在培养物中扩增作为心脏修复的细胞来源。该建议基于广泛的基础和临床前数据，支持MSC和心脏干细胞（CSC）用于细胞心肌成形术的价值。该方法的一个主要优势是我们能够从活检标本中制备足够数量的心脏干细胞用于治疗应用。这一办法有三个方面，具有很大的协同作用。首先，在项目1中，将基于现有的广泛的临床前数据库、已建立的人体安全性记录和已计划的急性心肌梗死患者临床试验，在缺血性心肌病患者的临床试验中探索MSC。其次，我们将同时在项目2中继续表征从人类获得的CSC，并进行相关的临床前实验。最后，基于在项目1中获得的大量经验，开发了递送技术和疗效监测，以及在项目2中完善的细胞方法，我们将在项目3中进行CSC的临床试验。总之，该计划将有能力进行高度相关和临床信息试验，这些试验将由基础细胞生物学的最新进展指导和完善。