Closed-Chest Cell Injections into Mouse Myocardium Targeted by Ultrasound

超声波靶向小鼠心肌闭胸细胞注射

• 批准号: 7121967
• 负责人: MATTHEW Lawrence SPRINGER
• 金额: $ 7.4万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7121967
• 关键词: SCID mouse; bioimaging /biomedical imaging; bone marrow; cell differentiation; cell transplantation; echocardiography; fluorescent dye /probe; heart imaging /visualization /scanning; laboratory mouse; microcapsule; musculoskeletal regeneration; myoblasts; myocardium; ultrasound

DESCRIPTION (provided by applicant): Intramyocardial cell implantation and injection of therapeutic genes have been proposed as therapies for ischemic heart disease. However, the recent literature contains numerous contradictory results. Different research groups inject identical cell populations into mouse hearts and report disparate findings, ranging from improvement of cardiac function to lack of improvement and absence of differentiated stem cells. This proposal is designed to evaluate the hypothesis that these contradictions stem, in part, from varying success of injection into the myocardial wall rather than the left ventricular cavity, and that non-invasive imaging with high resolution echocardiography can accurately target injections into normal and infarcted mouse hearts, providing a clinically relevant system with which to study potential cell implantation and gene therapies. First, a mixture of echocardiography contrast agent and fluorescent microspheres will be injected to correlate the observed needle position during echo-guided injections with the actual injection site as evidenced by histological examination. After the system has been optimized, high resolution echocardiography will be used to guide transthoracic implantations of labeled cells into the hearts of surgically infarcted mice, targeting the infarct border zone and demonstrating proof of concept. The system will be used to study the ability of labeled bone marrow derived cells to migrate through cardiac muscle to damaged tissue by targeted injections of labeled cells mixed with fluorescent microspheres of different sizes and colors. It will also be used to compare the effects of intramyocardial cell implantation during the infarction procedure to implantation several days after infarction, a more clinically relevant model that is very difficult to achieve without echo-guidance; as well as at multiple times. This will lead to further studies of targeted injection into the infarct border zone of both bone marrow-derived cells and myoblasts expressing growth factors. RELEVANCE: The implantation of so-called adult stem cells and the injection of genes encoding growth factors are potential treatments for poor cardiac function that typically plagues heart attack survivors. Many experiments can be carried out in mice; however, their hearts are so small that it is difficult to inject into them in a clinically relevant way. This research will use high-resolution ultrasound to guide such injections into the mouse heart, without surgery, and will make the mouse a much better model for such experiments.

描述（由申请人提供）：已经提出了心脏内部细胞的植入和注射治疗基因作为缺血性心脏病的疗法。但是，最近的文献包含许多矛盾的结果。不同的研究组将相同的细胞群体注入小鼠心脏并报告不同的发现，从心脏功能的改善到缺乏改善和缺乏分化干细胞。该提案旨在评估以下假设：这些矛盾部分是由于注射成功到心肌壁而不是左心室腔，并且具有高分辨率超声心动图的非侵入性成像可以准确地靶向正常和梗塞的注射小鼠心脏，提供与临床相关的系统，用于研究潜在的细胞植入和基因疗法。首先，将注入超声心动图造影剂和荧光微球的混合物，以将回声引入的注射期间观察到的针头与实际注射部位相关联，这是组织学检查所证明的。优化系统后，高分辨率超声心动图将用于引导标记的细胞的经胸腔植入到手术梗塞的小鼠的心脏中，以梗塞边界区域为目标并证明概念证明。该系统将用于研究标记的骨髓衍生细胞通过心脏肌肉迁移到受损组织的能力，该细胞的有针对性注射被带有不同尺寸和颜色的荧光微球混合的标记细胞。它也将用于比较梗塞过程中心脏内心脏细胞植入的影响与梗塞几天后的植入，这是一个更临床相关的模型，在没有回声引导的情况下很难实现。以及多次。这将导致进一步研究靶向注射到骨髓衍生细胞和表达生长因子的肌细胞的梗塞边界区域。相关性：所谓的成年干细胞的植入和编码生长因子的基因注射是对心脏功能不良的潜在治疗方法，通常会困扰心脏病发作幸存者。许多实验可以在小鼠中进行。但是，他们的内心很小，以至于很难以临床相关的方式注入它们。这项研究将使用高分辨率超声引导对小鼠心脏的注射，而无需手术，并且将使小鼠成为此类实验的更好模型。