Mesenchymal Stem Cell Cardiomyoplasty

间充质干细胞心肌成形术

• 批准号: 7081882
• 负责人: Joshua M Hare
• 金额: $ 97.56万
• 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: 2005-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7081882
• 关键词: auxiliary heart prosthesis; bone marrow; cardiac myocytes; cardiogenesis; cardiovascular stress test; cell differentiation; circulatory assist; clinical research; clinical trial phase I; clinical trial phase II; computed axial tomography; disease /disorder model; electrophysiology; heart failure; heart function; hematopoietic stem cells; hematopoietic tissue transplantation; human subject; human therapy evaluation; magnetic resonance imaging; mesenchyme; myocardial infarction; myocardium disorder; nonhuman therapy evaluation; patient oriented research; swine

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.

该细胞治疗专业中心提案旨在开发细胞心肌成形术来治疗缺血性心脏病，包括心肌梗塞后左心室功能障碍以及慢性缺血性心肌病。目前，人们对开发基于细胞的疗法来治疗心肌缺血性损伤引起的疾病抱有极大的热情。动物模型取得了快速进展，初步临床试验表明，急性和慢性心脏病的心功能可能得到改善。目前，骨髓仍然是心脏修复前体细胞的一个非常有前景的来源。我们的团队与 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即将启动该细胞类型的首次临床试验对于患有心肌梗塞的人。此外，现已鉴定出心脏干细胞可以在培养物中扩增，作为心脏修复的细胞来源。这个提议 基于广泛的基础和临床前数据，支持 MSC 和心脏干细胞 (CSC) 在细胞心肌成形术中的价值。该方法的主要优点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。该方法具有三重作用，具有显着的协同作用。首先，在项目1中，将基于现有广泛的临床前数据库、已建立的人体安全记录以及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间充质干细胞。其次，我们将同时在项目2中继续表征从人体获得的CSC并进行相关的临床前实验。最后，基于项目1中开发的递送技术和疗效监测方面获得的丰富经验，以及项目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。 该计划将有能力进行高度相关且临床信息丰富的试验，这些试验将受到基础细胞生物学最新进展的指导和完善。