Sustained release of targeted cardiac therapy with a replenishable implanted epicardial reservoir

Citation:

Whyte W, Roche ET, Varela CE, Mendez K, Islam S, O'Neill H, Weafer F, Shirazi RN, Weaver JC, Vasilyev NV, et al. Sustained release of targeted cardiac therapy with a replenishable implanted epicardial reservoir. Nat Biomed Eng. 2018;2 (6) :416-428.

Date Published:

2018 Jun

Abstract:

The clinical translation of regenerative therapy for the diseased heart, whether in the form of cells, macromolecules or small molecules, is hampered by several factors: the poor retention and short biological half-life of the therapeutic agent, the adverse side effects from systemic delivery, and difficulties with the administration of multiple doses. Here, we report the development and application of a therapeutic epicardial device that enables sustained and repeated administration of small molecules, macromolecules and cells directly to the epicardium via a polymer-based reservoir connected to a subcutaneous port. In a myocardial infarct rodent model, we show that repeated administration of cells over a four-week period using the epicardial reservoir provided functional benefits in ejection fraction, fractional shortening and stroke work, compared to a single injection of cells and to no treatment. The pre-clinical use of the therapeutic epicardial reservoir as a research model may enable insights into regenerative cardiac therapy, and assist the development of experimental therapies towards clinical use.