Abstract
BackgroundThe safety and efficacy of cardiac stem/progenitor cells (CSC) have been demonstrated in previous preclinical and clinical assays for heart failure. However, their optimal delivery route to the ischemic heart has not yet been assessed. This study was designed to determine by a non-invasive imaging technique (PET/CT) the biodistribution and acute retention of allogeneic pig CSC implanted by two different delivery routes, intracoronary (IC) and intramyocardial (IM), in a swine preclinical model of chronic ischemia–reperfusion.MethodsIschemia–reperfusion was induced in six Goettingen hybrid minipigs by 90 min coronary artery occlusion followed by reperfusion. Thirty days later, animals were allocated to receive IC (n = 3) or NOGA®-guided IM injection (n = 3) of 50 million of 18F-FDG/GFP-labeled allogeneic pig CSC. Acute retention was quantified by PET/CT 4 h after injection and cell engraftment assessed by immunohistochemical quantification of GFP+ cells three days post-injection.ResultsBiodistribution of 18F-FDG-labeled CSC was clearly visualized by PET/CT imaging and quantified. No statistical differences in acute cell retention (percentage of injected dose, %ID) were found in the heart when cells were administered by NOGA®-guided IM (13.4 ± 3.4%ID) or IC injections (17.4 ± 4.1%ID). Interestingly, engrafted CSC were histologically detected only after IM injection.ConclusionPET/CT imaging of 18F-FDG-labeled CSC allows quantifying biodistribution and acute retention of implanted cells in a clinically relevant pig model of chronic myocardial infarction. Similar levels of acute retention are achieved when cells are IM or IC administered. However, acute cell retention does not correlate with cell engraftment, which is improved by IM injection.
Highlights
The safety and efficacy of cardiac stem/progenitor cells (CSC) have been demonstrated in previous preclinical and clinical assays for heart failure
Pig cardiac stem/progenitor cells isolation and characterization Pig CSC were isolated from the cardiac tissue of Gottingen pigs and maintained in culture as previously reported [6]
Radiolabeling of CSCs with 18F‐FDG Radiolabeling did not induce a significant change in cell viability (−2 ± 4.6% of variation between CSC incubated with 2-deoxy-2-[18F] fluoro-d-glucose (18F-FDG) and control cells)
Summary
The safety and efficacy of cardiac stem/progenitor cells (CSC) have been demonstrated in previous preclinical and clinical assays for heart failure. Among the different cell types employed, cardiac stem/progenitor cells (CSC) have demonstrated a remarkable potential to induce a beneficial effect after implantation in rodent and pig models of myocardial infarction (MI) [4,5,6] Their therapeutic effect has been shown in a clinical trial performed in patients with heart failure [7]. Delivery of stem cells either by an intracoronary (IC) route or directly by intramyocardial injection (IM) has been associated with different degrees of cell retention (reviewed in [3]) In this sense, the use of three-dimensional electromechanical mapping (NOGA®) as a delivery system that allows targeting to the viable myocardium could favor cell engraftment [9, 10] and could be of great use specially in the case of those patients where the coronary artery might be blocked impeding an IC delivery
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