Cell retention and biodistribution after transendocardial delivery in cardiovascu

心血管经心内膜递送后的细胞保留和生物分布

• 批准号: 8054145
• 负责人: Didier B Rouy
• 金额: $ 13.66万
• 依托单位: BIOCARDIA, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8054145
• 关键词: Autologous; Autopsy; Back; Biodistribution; Bone Marrow; Cardiac; Cardiovascular system; Catheters; Cell Therapy; Cell Transplantation; Cells; Chemotactic Factors; Chest; Clinical; Control Animal; Coronary artery; Development; Devices; Distal; Drug Kinetics; Drug or chemical Tissue Distribution; Family suidae; Foundations; Future; Gene Proteins; Growth Factor; Heart; Heart failure; Image; Infarction; Injection of therapeutic agent; Label; Mediating; Methodology; Modeling; Mononuclear; Myocardial Infarction; Myocardial Ischemia; Myocardium; Needles; Operative Surgical Procedures; PET/CT scan; Pathology; Pattern; Phase; Positron-Emission Tomography; Process; Radiolabeled; Recovery of Function; Regenerative Medicine; Relative (related person); Research; Research Design; Research Methodology; Route; Safety; Shapes; Site; System; Technology; Therapeutic; Therapeutic Agents; Therapeutic Effect; Time; Ventricular; Work; base; heart function; improved; in vivo; injured; novel; radiotracer; safety study; success; tissue regeneration

DESCRIPTION (provided by applicant): Overview Over the past few decades, cell transplantation therapies have shown positive signs of efficacy and relative safety for tissue regeneration and functional recovery of myocardial infarction and ischemic heart failure. However, more than 95% of the cells infused in the coronary arteries are lost and successful retention of therapeutic cells in the target sites after delivery remains a major shortcoming to this approach. BioCardia has developed a helical needle-based catheter technology that enables accurate and controlled injection of various deliverables into targeted sites in the myocardium and that has great promise for increasing retention compared to straight needle-based direct or catheter delivery into target zones in the myocardium. Description The proposal here seeks to advance the field of cell therapy by demonstrating that compared to direct surgical delivery using straight needle, catheter-mediated transendocardial delivery using a helical shaped needle shows efficient delivery and superior retention of cell based therapeutics in healthy and post-myocardial infarction swine models. The objectives of this study are to compare cell retention rates and biodistribution when injected intramyocardially through BioCardia helical needle-tipped transendocardial delivery catheter with a helical tip versus when injected intramyocardially directly using a straight needle. If increased retention is observed, it will justify future transendocardial clinical development of cell based therapies that are currently being administered with a transepicardial approach and the increased value of having a helical tip at the distal end of the delivery catheter. A phase 2 will elaborate on these results to include a large pharmacokinetics study, a long term safety study and an efficacy study using autologous bone marrow mononuclear cells. This will lay the foundation for further clinical development of a combination treatment using the helical needle catheter and autologous bone marrow mononuclear cells. Research Design and Methods Autologous mononuclear cells will be purified from swine bone marrow, radiolabeled with 18F-FDG and delivered in healthy and post-myocardial infarction swines using both BioCardia transendocardial helical needle delivery device, and an open chest straight needle epicardial delivery process in order to compare cell retention rates. Biodistribution of the injected 18F-FDG-MNCs will be quantified by whole body PET-CT scan in vivo, and the injection sites within the heart will be identified and validated post necropsy. PUBLIC HEALTH RELEVANCE: Cell transplantation is one of the emerging strategies in novel cardiovascular therapies for restoring heart function in heart failure or after myocardial infarction. This research seeks to improve on the current delivery technologies which include delivery using a straight needle by increasing cell retention via their delivery using a novel intramyocardial helical needle tipped catheter. This research work could have critical implications in greatly improving the therapeutic effects of consistent targeting and trapping cells to specific sites within the injured heart and could provide a means to avoid back leak into the ventricular chamber while allowing for safe and efficient delivery of therapeutic agents including cells but also proteins, genes and other agents in the field of regenerative medicine.

描述（由申请人提供）：概述在过去的几十年中，细胞移植疗法在心肌梗死和缺血性心力衰竭的组织再生和功能恢复方面显示出积极的功效和相对安全性。然而，超过 95% 的注入冠状动脉的细胞会丢失，并且治疗细胞在递送后成功保留在目标部位仍然是这种方法的主要缺点。 BioCardia 开发了一种基于螺旋针的导管技术，能够将各种输送物准确、受控地注射到心肌的目标部位，与基于直针的直接或导管输送到心肌的目标区域相比，该技术有望提高保留率。描述 该提案旨在通过证明与使用直针的直接手术递送相比，使用螺旋形针的导管介导的经心内膜递送在健康和心肌梗塞后猪模型中显示出有效的递送和基于细胞的治疗的优异保留来推进细胞治疗领域。本研究的目的是比较通过带有螺旋尖端的 BioCardia 螺旋针头经心内膜输送导管进行心肌内注射与使用直针直接进行心肌内注射时的细胞保留率和生物分布。如果观察到保留增加，则将证明目前正在采用经心外膜方法进行的基于细胞的疗法的未来经心内膜临床开发以及在输送导管远端具有螺旋尖端的价值增加。第二阶段将详细阐述这些结果，包括一项大型药代动力学研究、一项长期安全性研究和一项使用自体骨髓单核细胞的功效研究。这将为螺旋针导管和自体骨髓单核细胞联合治疗的进一步临床开发奠定基础。研究设计和方法将从猪骨髓中纯化自体单核细胞，用 18F-FDG 放射性标记，并使用 BioCardia 经心内膜螺旋针输送装置和开胸直针心外膜输送过程输送到健康猪和心肌梗塞后猪体内，以比较细胞保留率。注射的 18F-FDG-MNC 的生物分布将通过体内全身 PET-CT 扫描进行量化，并且心脏内的注射部位将在尸检后进行识别和验证。 公共卫生相关性：细胞移植是新型心血管疗法中用于恢复心力衰竭或心肌梗死后心脏功能的新兴策略之一。这项研究旨在改进当前的输送技术，包括使用直针输送，通过使用新型心肌内螺旋针尖导管输送来增加细胞保留。这项研究工作可能对大大提高一致靶向和捕获细胞到受伤心脏内特定部位的治疗效果具有重要意义，并且可以提供一种避免回渗到心室的方法，同时允许安全有效地输送治疗剂，包括细胞、蛋白质、基因和再生医学领域的其他药物。