Cell retention and biodistribution after transendocardial delivery in cardiovascu

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 needleshows 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 throughBioCardia 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 developmentof 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 helicalneedle 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 andefficient delivery of therapeutic agents including cells but also proteins, genes and other agents in the field of regenerative medicine.