Engineering of Pacemaker Tissue for Cardiac Implantation

描述(申请人提供)：先天性和外科手术引起的房室结传导阻滞是一种严重的长期临床症状。 儿科病人的问题。目前，永久性植入一种 心脏起搏器是治疗心脏起搏器疾病的唯一方法。 先天性完全性心脏传导阻滞合并房室传导阻滞 先天性心脏畸形，如室间隔缺陷，房室管缺陷， 和法洛四联症。尽管心脏领域的技术进步 起搏器的设计和功能，永久性起搏器在婴儿和儿童中的治疗 儿童仍然是个问题。因为儿童的存活率 接受复杂的外科手术修复先天性心血管缺陷 已经大大增加，对改进的长期起搏解决方案的需求 儿科患者群体为这一项目提供了理论基础。 该项目的主要目标是将组织工程化为 从心房到心室的电导管，用于 缺乏正常房室结功能的耐心。工程化的组织将是 由骨骼肌祖细胞(成肌细胞)或间充质干细胞组成 可自体衍生的细胞(骨髓基质细胞)。这些细胞 将被铸造在使用天然聚合物的三维组织结构中， 例如胶原，以便有效地将细胞输送到眼部的房室沟 心。 因此，在本提案中，我们将处理以下具体问题 AIMS；(A)设计适合心脏的导电组织 实施(B)表征工程化的机电性能 体外构建组织，(C)确定植入组织的实用性 (D)评估心脏房室沟的导电性。 植入了工程化组织结构的心脏。 这是一个概念简单的研究项目，需要广泛的 在多个领域的专业知识，包括细胞生物学、组织工程和 电生理学。这项研究的成功有赖于多学科的 将他们的知识应用于特定组件的一组个人 该项目的目的是开发一种治疗方法来缓解 严重的临床问题。归根结底，这些实验旨在 为传统心脏起搏器提供替代或辅助治疗 心理治疗。

DESCRIPTION (Provided by Applicant): Congenital and surgically-induced block of cardiac atrioventricular (AV) node conduction is a serious long-term clinical problem in pediatric patients. Currently, the permanent implantation of a cardiac pacemaker device is the only therapy available for the treatment of congenital complete heart block and AV block subsequent to surgical repair of inborn heart abnormalities such as ventricular septal defect, AV canal defect, and tetralogy of Fallot. Despite the technological advancements in cardiac pacemaker design and function, permanent pacemaker therapy in infants and children continues to be problematic. Since the survival rate for children that undergo complex surgical procedures to repair congential cardiovascular defects has greatly increased, the need for improved long-term pacing solutions in the pediatric patient population has provided the rationale for this project. The primary goal of the project is to engineer tissue that would act as an electrical conduit from the atrium to the ventricle of the heart for use in patience that lack normal AV node function. The engineered tissue will be comprised of skeletal muscle progenitor cells (myoblasts) or mesenchymal stem cells (bone marrow stromal cells) that can be autologously derived. The cells will be cast in a three dimensional tissue construct using natural polymers, such as collagen, in order to efficiently deliver cells to the AV groove of the heart. Accordingly, in the present proposal, we will address the following specific aims; (a) engineer electrically conductive tissue suitable for cardiac implementation (b) characterize the electromechanical properties of engineered tissue constructs in vitro, (c) determine the practicality of implanting tissue constructs in the cardiac AV groove, and (d) evaluate electrical conduction in hearts implanted with engineered tissue constructs. This is a conceptually simple research project that requires extensive expertise in a number of fields including cell biology, tissue engineering, and electrophysiology. The success of the research depends on a multidisciplinary group of individuals that will apply their knowledge to specific components of the project with the intention of developing a therapy to alleviate a substantial clinical problem. Ultimately, these experiments are intended to provide an alternative or adjunct treatment to conventional cardiac pacemaker therapy.