Myocardial substrate and route of administration determine acute cardiac retention and lung biodistribution of cardiosphere-derived cells

Background. Quantification of acute myocardial retention and lung bio-distribution of cardiosphere-derived cells (CDCs) following transplantation is important to improve engraftment. Methods and results. We studied acute(1 hour) cardiac/lung retention in 4 groups (n 5 25) of rats (normal-NL, acute ischemia-reperfusion-AI-RM, acute permanent ligation-PL, and chronic infarct by ischemia-reperfusion-CI-R) using intra-myocardial delivery, 1 group using intracoronary delivery (acute ischemia-reperfusion, AI-RC, n 5 5) and 1 group using intravenous delivery (acute ischemia-reperfusion, AI-RV, n 5 5) of CDCs by PET. Cardiac retention was similar in the NL, AI-RM, CI-R, and A-IRC groups (13.6% ± 2.3% vs 12.0% ± 3.9% vs 9.9 ± 2.8 vs 15.4% ± 5.5%; P 5 NS), but higher in PL animals (22.9% ± 5.2%; P < .05). Low cardiac retention was associated with significantly higher lung activity in NL and AI-RM groups (43.3% ± 5.6% and 39.9% ± 9.3%), compared to PL (28.5% ± 5.9%), CI-R (20.2% ± 9.3%), and A-IRC (19.9% ± 5.6%) animals (P < .05 vs AI-RM and NL). Lung activity was highest following intravenous CDC delivery (55.1% ± 9.3%, P < .001) and was associated with very low cardiac retention (0.8% ± 1.06%). Two-photon microscopy indicated that CDCs escaped to the lungs via the coronary veins following intra-myocardial injection. Conclusions. Acute cardiac retention and lung bio-distribution vary with the myocardial substrate and injection route. Intra-myocardially injected CDCs escape into the lungs via coronary veins, an effect that is more pronounced in perfused myocardium.