Abstract 1080: Myocardial Substrate Determines Acute Cardiac Retention and Lung Biodistribution of Intramyocardially Injected Cardiac-Derived Stem Cells - A PET/CT Experimental Study
Stem cell transplantation studies consistently reveal low engraftment rates and marginal long term functional benefit. In vivo cell tracking following transplantation is essential to improving the success of stem cell therapy.
Aim: To assess the impact of the myocardial substrate on acute cardiac retention and lung biodistribution of intramyocardially injected cardiac-derived stem cells (CDCs), using in vivo PET/CT.
Methods: Two million 18FDG (2μCi/mL) labeled CDCs from syngeneic, male Wistar Kyoto rats were injected into acutely infarcted myocardium of female recipients. We studied 3 groups of rats by PET/CT (1hr after cell injection):
non-infarcted normal (NL group, n=3),
infarcted (permanent ligation of the left coronary artery - PL group, n=7),
infarcted (45 min of ischemia followed by reperfusion -I/R group, n=9).
13NH3 PET and CT were performed for myocardial delineation, coregistration and attenuation correction, respectively. In 14 additional animals (PL and I/R groups), CDC biodistribution (1hr after injection) was measured by quantitative PCR for the male-specific SRY gene.
Results: Injected cells were identified as bright spots in the heart (within an area of perfusion deficit) and the lungs, by 18FDG PET. Cell retention (% of net injected activity) in the heart at 1h, by PET, was similar in the NL and I/R groups (13.6±2.3% vs 12.0±3.9%; P=NS), but higher in PL animals (22.9±5.2%; P<0.05 vs NL and I/R). The low cardiac retention was associated with significantly higher lung activity in the NL and IR groups (43.3± 5.6 and 39.9±9.3 respectively), compared to 28.5±5.9 in the PL group (P<0.05). PCR confirmed higher numbers of CDCs in the lungs than the heart in the IR compared to PL group; ratio of cell number in heart to lungs was 0.63±0.18 in the IR group and 3.33±3.2 in the PL group; P<0.05. The rapid egress of CDCs from the myocardium into the lungs was confirmed to be via the coronary veins by fluorescent microscopy (n=4), performed after Di-I labeling of CDCs and thioflavin S labeling of the vasculature.
Conclusions: Acute cardiac retention varies with the myocardial substrate. Large numbers of intramyocardially injected CDCs escape into the lungs acutely via the coronary venous system, an effect that is more pronounced in perfused myocardium.