Abstract 5280: Positron Emission Tomography (PET) for In Vivo Quantification and Optimization of Acute Cell Retention after Intramyocardial Cardiac-Derived Stem Cell Delivery

Abstract

Success of stem cell transplantation for cardiac regeneration is partially limited by low retention/engraftment of the delivered cells. A clinically applicable method for accurate quantification of cell retention would enable optimization of cell delivery. To quantify acute myocardial retention and identify strategies that improve retention following intramyocardial injection of cardiac-derived stem cells (CDCs). Two million CDCs derived from syngeneic, male Wistar Kyoto (WK) rats were labeled with 18 FDG (2μCi/mL) and injected intramyocardially into the ischemic region of female WK rats (n=43) immediately following permanent left coronary artery ligation. The effects of fibrin glue, local 2,3-butanedione-2-monoxime (BDM, an excitation-contraction uncoupler), bradycardia (adenosine) and cardiac arrest were examined. 18 FDG PET images were coregistered with myocardial perfusion 13 NH 3 images for myocardial delineation, and with chest CT images for attenuation correction. Quantitative PCR for the male-specific SRY gene was performed in 6 control animals to validate the PET results. Myocardial cell retention 1 hr after cell delivery in control animals was 17.6±11.5% (n=6) by quantitative PCR, and 17.8±7.3% (n=7) by PET. When CDCs were injected immediately following induction of cardiac arrest (n=4), retention was greatly increased to 75.6±18.6% ( P <0.001), suggesting a role for cardiac contraction, heart rate and/or coronary flow on CDC retention. Adenosine slowed the ventricular rate and doubled CDC retention (35.4±5.3%, n=4, P <0.05). A similar increase in CDC retention was observed following epicardial application of fibrin glue at the injection site (37.5±8.2%; n=8, P <0.01). The combination of fibrin glue and adenosine further improved CDC retention to 39.0±11.6% (n=8, P <0.001). Local BDM treatment transiently suppressed contractility at the injection site (by visual inspection), but did not affect CDC retention (14.9 ±6.9%, P =ns). In vivo PET permits accurate measurement of CDC retention early after intramyocardial delivery. Sealing injection sites with fibrin glue may be a clinically translatable method for improving stem cell engraftment in a beating heart.