Cellular Cardiomyoplasty for Acute and Chronic Ischemic

描述(由申请人提供)： 这项专门的细胞治疗中心的提案旨在开发细胞心肌成形术，用于治疗缺血性心脏病，包括心肌梗死后左心功能不全以及慢性缺血性心肌病。目前，对于心肌缺血性损伤引起的疾病，人们对基于细胞的治疗方法的开发异常热情。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会得到改善。目前，骨髓仍然是一种非常有希望的心脏修复前体细胞来源。我们团队一直与Osiris Treeutics合作开发用于细胞性心肌成形术的骨髓间充质干细胞(MSCs)，这项工作的结果导致即将启动针对患有心肌梗死的人类的首个此类细胞的临床试验。此外，现已鉴定出可在培养中扩增的心脏干细胞，作为心脏修复细胞的来源。这一建议基于大量的基础和临床前数据，支持MSCs和心脏干细胞(CSCs)在细胞性心肌成形术中的价值。该方法的一个主要优点是我们有能力从活检标本中制备足够数量的心脏干细胞，用于治疗应用。这种方法有三个方面，具有很大的协同效应。首先，在项目1中，MSCs将在基于现有的广泛的临床前数据库、在人类中建立的安全性记录以及针对急性心肌梗死患者的已经计划的临床试验的基础上，在人类缺血性心肌病的临床试验中进行探索。第二，我们将同时在项目2中继续鉴定从人类获得的干细胞，并进行相关的临床前实验。最后，基于项目1中开发的输送技术和疗效监测的大量经验，以及项目2中完善的细胞方法，我们将在项目3中进行CSCs的临床试验。该计划将有能力进行高度相关和临床信息丰富的试验，这些试验将由基础细胞生物学的最新进展指导和完善。

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.