Safety and efficacy of a novel catheter system for transcoronary delivery of medications and stem cell-based therapies to myocardium

Background Myocardial uptake of cell-based therapies is a sine-qua-non condition for achieving therapeutic effects in the myocardium. Minimally-invasive cell administration techniques (such as intracoronary stop-flow administration or intravenous infusion) have yielded very poor myocardial uptake (≈1-3% administered cells); a critical limitation to the progress of the field. Purpose We evaluated safety and efficacy of a novel catheter system (Circulate Catheter) for transcoronary delivery of medications and cell-based therapies that we designed (academic setting) to overcome major limitations of prior cell-delivery systems. The catheter consists of a cell product suspension reservoir and a system of controlled transcoronary delivery while maintaining coronary perfusion. Methods The Circulate system was employed in patients with non-ischemic cardiomyopathy (n=10, age 40-65 years) to administer 30x106 standardized umbilical cord-derived mesenchymal stem cells (Cardiocell Advanced Therapy Medicinal Product, ATMP). 50% of the cells were labeled with 99mTc-extametazime (Ceretec, GE Heatltcare; 99mTc T1/2≈6h). Prior to Cardiocell administration, the effect of nitroglycerin (GTN, 200µg) administration via the Circulate Catheter was evaluated. After washout, Cardiocell suspension (total volume of 20mL) was delivered split into 3 main coronary arteries. Myocardial uptake of the cell label was detected at 60 min on a whole-body single-photon emission computed tomography (example in Fig. 1). Results No delivery catheter-related and no drug/ATMP administration-related complications occurred. GTN application via the Circulate Catheter resulted in 30.9(21-44)% increase in distal coronary diameter (angiographic corelab analysis). Myocardial uptake of Cardiocell was 28.04(23.3-32)%. No clinical complications occurred by 30-days and 12-months. Left ventricular ejection fraction was 33.8(27-39)% at baseline and 35.1(28-42)% at follow-up. Conclusion Myocardial delivery of cell-based ATMP via a dedicated non-occlusive transcoronary catheter system is safe and is associated with an unprecedented myocardial uptake of the cell label, exceeding by ≈10-fold that achievable with prior techniques. This opens a new pathway for randomized clinical trials.